International Conference on

Cancer Therapy

Scientific Program

Keynote Session:

Meetings International -  Conference Keynote Speaker Jonathan Sprent photo

Jonathan Sprent

Garvan Institute of Medical Research, Australia

Title: Strong immunogenicity of membrane nanovesicles from dendritic cells

Biography:

After a PhD at the Walter Eliza Hall Institute in Melbourne and post-docs in Switzerland and UK, Jonathan Sprent worked for 30 years in the USA, first at the University of Pennsylvania in Philadelphia and then at The Scripps Research Institute in San Diego. During this time he worked on many aspects of T cell biology, including T-B collaboration during antibody production, role of T cells in graft-versus host disease after bone marrow transplantation, positive and negative selection during T cell differentiation in the thymus, T cell survival and homeostasis of mature T cells, construction of artificial antigen-presenting cells (APC) from insect cells, and the use of monoclonal antibodies (mAb) to enhance and target the activity of IL-2 and other cytokines. Jonathan moved from the USA in 2006 to form a research group at the Garvan Institute where he has continued to work on T cell differentiation and function. The lab is supported by several NHMRC grants and has collaborative interactions with many other investigators, both nationally and internationally. Awards: Fellow of the Royal Society Fellow of the Australian Academy Honorary Member, British Society of Immunology Honorary Member, Korean Association of Immunologists J.Allyn Taylor International Prize in Medicine 1998 President of the American Association of Immunologists Merit Award x 2 NIH Burnet Award NHMRC SPRF NHMRC Achievement Award NHMRC.

Abstract:

Interest in cancer immunotherapy has been bolstered by the recent success of T cell checkpoint blockade with specific antibodies. This approach might be especially effective if combined with methods for enhancing tumor immunogenicity, eg injection of dendritic cells (DC) expressing tumor antigens. Currently, DC therapy is successful in only a small proportion of patients, perhaps reflecting poor homing of injected DC. To overcome this problem, we have generated cell-surface membrane nanovesicles from in vitro-generated bone-marrow-derived mature DC. When loaded with specific peptide, the vesicles are stimulatory for naïve TCR transgenic CD8 T cells in vitro without APC, though only with aggregated vesicles and not with vesicles dispersed into nano-vesicles by sonication. By contrast, after IV injection in vivo, the nanovesicles are much more immunogenic than aggregates and generate strong proliferation and effector function of CD8 cells in both spleen and LN, reflecting widespread distribution of the vesicles and uptake by host APC. Preliminary work has shown that injection of the vesicles can be used vaccinate against tumor growth and also reject established tumours in mice.

Meetings International -  Conference Keynote Speaker Hong Qin photo

Hong Qin

Beckman Research Institute of the City of Hope, USA

Title: Novel Immunotherapies targeting BAFF-receptor for drug-resistant B-cell lymphoma and leukemia

Biography:

Dr. Hong Qin currently serves as Associate Professor in the Toni Stephenson Lymphoma Center at City of Hope in Duarte, California and he has been developing novel immunotherapies for over 15 years. Since completing his PhD in 2003 at the University of Western Ontario, Canada and post-doctoral fellowship in 2008 at MD Anderson Cancer Center in Huston, Texas, Dr. Qin has demonstrated his broad experience in immunology by developing cancer vaccine, monoclonal antibody, and CAR-T cell therapies.

Abstract:

Monoclonal antibody (mAb) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising clinical outcomes treating hematological malignancies. However, disease relapse remains problematic and likely caused by loss of therapeutic targets on tumors.1 Thus, novel immunotherapies against alternative targets are urgently needed. We developed a new therapeutic mAb against B-cell activating factor receptor (BAFF-R), a tumor necrosis factor primarily expressed on B cells and B-cell lymphoma and leukemia.2 The mAb induced antibody-dependent cellular cytotoxicity against a panel of human B-cell tumor lines and primary tumors including samples from relapse after rituximab treatment. Potent in vivo antitumor effects were observed on two drug-resistant human lymphoma models (rituximab- and ibrutinibresistant lymphomas) resulting in eradication of implanted tumors and long-term, tumor-free survival (P<0.001).3 Adapting the antibody binding domain, we developed a BAFF-R CAR containing CD3 and 4-1BB intracellular signaling domains. BAFF-R CAR-T cells had significant activation and killing against various malignant B-cell lines and primary tumors (NHLs, acute lymphoblastic leukemias, and chronic lymphocytic leukemias), in vitro. Tumor eradication and tumor-free survival was repeatedly observed in human lymphoma xenograft models including mantle cell (JeKo-1, Z-138) and Burkitt (Raji) lymphomas in NSG mice (P<0.01). Moreover, our BAFF-R CAR-T therapy eradicated CD19KO Z-138 tumors that is resistant to CD19-CAR treatment in NSG mice (*P<0.01 Figure). Altogether, our results strongly support the translational significance of our novel BAFF-R targeting immunotherapies, particularly for the major unmet clinical need of drug-resistant relapses in B-cell lymphoma and leukemia. 

Meetings International -  Conference Keynote Speaker Veronica Ponce-Castaneda photo

Veronica Ponce-Castaneda

Instituto Mexicano del Seguro Social, Mexico

Title: Whole miRNOME perspective identify a critical 30 miRNA Core in retinoblastoma

Biography:

Professor in Department of Cell Biology at National Autonomous University of Mexico. Dr. Martha is a Medical Surgeon and Doctorate in Biomedical Sciences MD, Ph.D.
Subject of interests are Medicine, Molecular and Cellular Biology.

Abstract:

miRNAs have a prominent position in the negative control of gene expression and are involved in many cellular processes including carcinogenesis. Analysis and published results of high throughput miRNA profiles lack a robust approach to describe their findings with a real integrative approach. We examined the whole miRNome using a high throughput microarray platform including 2578 mature miRNAs in 12 samples of primary human retinoblastoma, an intraocular malignant tumor of early childhood and probably the most robust clinical model of genetic predisposition to develop cancer.This work delineates the miRNA landscape in human retinoblastoma samples with a non-biased approach using detection call scores as an approximation to expressed/not-expressed state for each miRNA. With this approach we discovered a central cluster of 30 miRNAs highly expressed in all the cases, a cluster of 993 not expressed in all cases and 1022 variably detected in the samples accounting for inter tumor heterogeneity. We further explored mRNA targets, pathways and biological processes affected by some of these miRNAs.The 30 miRs core represent a shared miRNA machinery in retinoblastoma affecting most pathways considered hallmarks of cancer. We identified miR-3613 as a potential down regulator hub, because is highly expressed by all the samples and has at least 36 tumor suppressor genes as potential mRNA targets including the RB1 gene itself. Our results indicate that human retinoblastoma share a common and fundamental miRNA expression profile regardless of heterogeneity.miRNAs have a prominent position in the negative control of gene expression and are involved in many cellular processes including carcinogenesis. Analysis and published results of high throughput miRNA profiles lack a robust approach to describe their findings with a real integrative approach. We examined the whole miRNome using a high throughput microarray platform including 2578 mature miRNAs in 12 samples of primary human retinoblastoma, an intraocular malignant tumor of early childhood and probably the most robust clinical model of genetic predisposition to develop cancer.This work delineates the miRNA landscape in human retinoblastoma samples with a non-biased approach using detection call scores as an approximation to expressed/not-expressed state for each miRNA. With this approach we discovered a central cluster of 30 miRNAs highly expressed in all the cases, a cluster of 993 not expressed in all cases and 1022 variably detected in the samples accounting for inter tumor heterogeneity. We further explored mRNA targets, pathways and biological processes affected by some of these miRNAs.The 30 miRs core represent a shared miRNA machinery in retinoblastoma affecting most pathways considered hallmarks of cancer. We identified miR-3613 as a potential down regulator hub, because is highly expressed by all the samples and has at least 36 tumor suppressor genes as potential mRNA targets including the RB1 gene itself. Our results indicate that human retinoblastoma share a common and fundamental miRNA expression profile regardless of heterogeneity.

Meetings International -  Conference Keynote Speaker Ivana Haluskova Balter photo

Ivana Haluskova Balter

CHD Group, France

Title: Vaccines and infectious diseases

Biography:

Ivana Haluskova Balter is a Medical and cosmopolitan professional specialized in infectious diseases and travel medicine, internal medicine covering various therapeutic axes, certified in Immunology and Pediatric, MBA vaccinology and years of clinical practice. Lived multi-country medical “field “experience in Southeast Asia (India in particular), West/Central/East Europe. Speaking French, English, Russian, Italian, Czech, Slovak with notion of Mandarin. Over 12 years of experience in pharmaceutical research and development for European and USA companies at global level. Active member of French immunology society (SFI) administrative board and several international  academic societies (focus on innovation of R&D reflecting immunology and genetic variability,  role of immunologic approach for treatment and diagnostic, tackle problem  of resistance for antimicrobials, antimalarial, antivirals etc). Member of advisory Health concern (India) and think tank group in order to attract attention to role of immunology, personalized and preventive medicine   and accurate diagnostic and   global cooperation in this area. Years of expertise to work globally within Europe, USA  but recently more focused on  BRICS - Asia (India in Particular) as a Medical advisor promoting partnership to bring science into clinic.

Abstract:

A vaccine is a biological preparation that improves immunity to a particular microorganism. The working principle is to stimulate the body's immune system to recognize the agent as foreign, destroy it, and "remember" it. Vaccines are recognized for highly potent tool of public health. Accurate diagnostic and surveillance with better understanding of genetic and immunologic background of host specific response and pathogen evolution drives adapted vaccine research. Pandemics, drug resistance and neglected diseases framing health as a “global security issue”.  The list was drawn up in a bid to guide and promote research and development (R&D) of new antibiotics, as part of WHO’s efforts to address growing global AMR (27th Feb 2017) and it highlights in particular the threat of gram-negative bacteria. Although initially omitted from the list, tuberculosis (MDR/XDR) and latent tuberculosis represent still a major issue to tackle. XDR tuberculosis has evolved in several tuberculosis endemic countries to drug incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). BCG vaccine successfully helped to interrupt transmission cycle and large reduction of mortality. HIV/AIDS has known link with tuberculosis but other risk factors have also emerged in recent years as important determinants of the TB epidemic, one of which is diabetes mellitus. Noted risk or new emerging and re-emerging pathogens originated from animals after having crossed the species barrier (e.g Ebola) and re-appearance of “old diseases” like pertussis, measles. Finally, neglected tropical diseases represent a vast area where innovative vaccines might have strong economic impact. Live attenuated vaccines elicit a broad immune response (humoral and cellular) and there is a strongly expected disease nonspecific effect to be looked in depth. This direction along with improving of host immune system capacities (known microbiota and immune cell “training” and immune cell metabolic profiling) seems to be a promising path to explore further.

Oral Session 1:

  • Workshop
Meetings International -  Conference Keynote Speaker Hong Qin photo

Hong Qin

Beckman Research Institute of the City of Hope

Title: Novel Immunotherapies targeting BAFF-receptor for drug-resistant B-cell lymphoma and leukemia

Biography:

Hong Qin currently serves as Associate Professor in the Toni Stephenson Lymphoma Center at City of Hope in Duarte, California and he has been developing novel immunotherapies for over 15 years. Since completing his PhD in 2003 at the University of Western Ontario, Canada and post-doctoral fellowship in 2008 at MD Anderson Cancer Center in Huston, Texas, Dr. Qin has demonstrated his broad experience in immunology by developing cancer vaccine, monoclonal antibody, and CAR-T cell therapies.

Abstract:

Monoclonal antibody (mAb) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising clinical outcomes treating hematological malignancies. However, disease relapse remains problematic and likely caused by loss of therapeutic targets on tumors.1 Thus, novel immunotherapies against alternative targets are urgently needed. We developed a new therapeutic mAb against B-cell activating factor receptor (BAFF-R), a tumor necrosis factor primarily expressed on B cells and B-cell lymphoma and leukemia.2 The mAb induced antibody-dependent cellular cytotoxicity against a panel of human B-cell tumor lines and primary tumors including samples from relapse after rituximab treatment. Potent in vivo antitumor effects were observed on two drug-resistant human lymphoma models (rituximab- and ibrutinibresistant lymphomas) resulting in eradication of implanted tumors and long-term, tumor-free survival (P<0.001).3 Adapting the antibody binding domain, we developed a BAFF-R CAR containing CD3 and 4-1BB intracellular signaling domains. BAFF-R CAR-T cells had significant activation and killing against various malignant B-cell lines and primary tumors (NHLs, acute lymphoblastic leukemias, and chronic lymphocytic leukemias), in vitro. Tumor eradication and tumor-free survival was repeatedly observed in human lymphoma xenograft models including mantle cell (JeKo-1, Z-138) and Burkitt (Raji) lymphomas in NSG mice (P<0.01). Moreover, our BAFF-R CAR-T therapy eradicated CD19KO Z-138 tumors that is resistant to CD19-CAR treatment in NSG mice (*P<0.01 Figure). Altogether, our results strongly support the translational significance of our novel BAFF-R targeting immunotherapies, particularly for the major unmet clinical need of drug-resistant relapses in B-cell lymphoma and leukemia. 

Oral Session 2:

  • Special Session

Oral Session 3:

  • Immunotherapy

Chair

Jonathan Sprent

Garvan Institute of Medical Research

Co-Chair

Hong Qin

Beckman Research Institute of the City of Hope

Meetings International -  Conference Keynote Speaker Chi-Ying Huang photo

Chi-Ying Huang

National Yang Ming University, Taiwan

Title: Drug repurposing: From big data to therapeutics

Biography:

Chi-Ying Huang has completed his PhD from Iowa State University and Postdoctoral Studies from School of Medicine, Stanford University, USA. He is the Professor of Institute of Biopharmaceutical Sciences, National Yang Ming University, Taiwan. He has published more than 140 papers in reputed journals.     

Abstract:

Of 71 anti-cancer drugs for solid tumors approved by the FDA between 2002 and 2014, the median gains in progression-free and overall survival are ~2 months. These observations suggest two potential unmet clinical needs: (1) the existence of drug resistance and (2) the importance of patient stratification. In other words, it is imperative to implement a companion diagnostic biomarker along with drug discovery pipeline. To address these two questions, we have accessed several big data to identify old drugs for anti-cancer drug discovery. Firstly, resistance to chemotherapy or targeted therapy is a major problem for systemic lung cancer treatment. Such resistance may be explained by cancer stem-like cell (CSC) theory. By using the Connectivity Map dataset, we have identified phenothiazine-like antipsychotic drugs which may reverse the CSC-associated gene expression. Further, the in vitro and in vivo experiments have validated its anti-CSC effects. This study demonstrated a novel platform for screening potential anti-CSC drugs, which may overcome the drug resistance. Secondly, synthetic lethality (SL) has emerged as a novel anti-cancer strategy. SL is an interaction between two genes such that simultaneous perturbations of two genes result in cell death or a dramatic decrease of cell viability, whereas a perturbation of either gene alone is not lethal. We evaluated several old oncology drugs and mapped their corresponding SL pairs. The predicted results were further validated via in vitro biochemical assay and retrospectively sequencing of patient specimens. In conclusion, this systematic analysis strategy could rapidly place old drugs with biomarkers for clinical study.

Meetings International -  Conference Keynote Speaker Lisa Oliver photo

Lisa Oliver

University of Nantes, France

Title: DECONSTRUCTION–RECONSTRUCTION of the tumour

Biography:

L. Oliver completed her PhD at the University of Paris VII, France. Presenting working in the group of Dr Francois Vallette at “Centre of Research in Cancer-Immunology Nantes-Angers”. She has published over 80 articles in reputed journals.   

Abstract:

Our group works on Glioblastoma Multiforme (GBM) tumours. In collaboration with neurosurgeons we obtain tumours from the tumorotheque, which are disassociated mechanically with the aim of recuperating all the cells present in the tumour. It is well known that the Glioblastoma consists of a heterogeneous cell population and our culture conditions allow for the proliferation and survival of all the cell types present in the original tumour. This first part would represent the deconstruction of the tumour and at present we have at our disposition a collection of 80 primary cultures of GBMs. Initial experiments have shown that in the present of “Cancer-associated Fibroblasts” or CAFs, tumour cells proliferate more and respond less to irradiation and temolozolamide (TMZ) (principal treatment for GBM). For the second part of our project namely the “reconstruction” we have developed a system of 3D-bioprinting, which would include adding a mixture of primary GBM cells and CAFs in a matrix of hydrogel and collagen that would represent our bioink. Using a 3D-bioprinter we would then reconstruct the tumour. The reconstructed tumour scaffolds should all be identical and contain similar cell numbers that are important in the analyses. Once tumour cell aggregates are visible in the scaffolds, these scaffolds would be used to determine the role of CAFs in the “protection – survival” of the tumour after chemo- (100 µM TMZ) and/or radiotherapy.

Meetings International -  Conference Keynote Speaker Jin-Mei Lai photo

Jin-Mei Lai

Fu-Chen Catholic University, Taiwan

Title: Zhen-Qi Sijunzi decoction can alleviate cisplatin-induced toxicity and prolong the survival time of cachectic mice by recovering muscle atrophy

Biography:

Upon completion of her doctorate in Biochemistry and Molecular Biology at the National Taiwan University in 2003, she stayed in the National Taiwan University for Postdoctoral training where she worked on the ROCK-mediated signaling pathway in phorbol ester-induced apoptosis. Dr. Lai joined the faculty of Department of Life Science, Fu-Jen Catholic University in Taiwan in 2004. She is currently an Associate Professor. At Fu-Jen University, Dr. Lai worked on the role of PBK/TOPK protein kinase in lung carcinogenesis and cancer therapeutics. Recently, she worked on the Chinese medicine in alleviating tumor- and/or cisplatin-induced cachexia.

Abstract:

Cachexia is a devastating clinical condition frequently associated with many types of cancers and is also a common consequence of chemotherapy administration. Based on the Traditional Chinese Medicine (TCM) theory, the formula empirically used as invigorators for treating weakness, fatigue and poor appetite are often used for improving cachectic conditions. However, comprehensive evidence to characterize the anti-cachexia mechanism of TCM remains largely needed. In this study, we employed Lewis lung carcinoma (LLC)-induced cancer cachectic mice model to demonstrate the anti-cachectic effect of a novel combination of decoction referred to as Zhen-Qi Sijunzi (ZQ-SJZ). Administration of ZQ-SJZ can recover tumor- and/or cisplatin-induced body weight loss, intestinal mucosal damage, as well as forelimb grip strength and myofiber size. Mechanistically, ZQ-SJZ increased the levels of myogenic proteins, such as MyHC and myogenin, and decreased the atrophy-related protein, atrogin-1 in cisplatin-treated C2C12 myotubes in vitro. Moreover, cisplatin-induced mitochondria dysfunction can be hampered by the co-administration of ZQ-SJZ, by which it recovered cisplatin-mediated decrease of PGC-1a and PKM1. Given that PGC-1a plays a role in both mitochondria biogenesis and myogenesis, ZQ-SJZ likely plays a role in the modulation of mitochondrial function and subsequent myogenesis. Notably, ZQ-SJZ administration significantly prolonged the survival of LLC-induced cachectic mice under cisplatin treatment, indicating its profound activity in anti-cachexia and chemo-toxicity alleviation. Taken together, these results demonstrated the anti-cachectic mechanism of ZQ-SJZ and its potential use as a palliative strategy to improve the efficacy of chemotherapy.

Meetings International -  Conference Keynote Speaker Song-Nan Chow photo

Song-Nan Chow

National Taiwan University Hospital, Taiwan

Title: Cancerous immunoglobulins and potential clinical applications

Biography:

Song-Nan Chow graduated from College of Medicine, National Taiwan University (NTU) in 1968(M.D.). He also got Ph.D. from Graduate Institute of Clinical Medicine, National Taiwan University in 1983. Dr. Chow served an internship at Maimonides Medical Center, New York City, USA during 1972-1973. He was a senior investigator in University of British Columbia, Vancouver, Canada and Eastern Virginia Medical School, Norfolk, USA during March 1984 to September 1984. Dr. Chow served as Professor and Head in Department of Obstetrics & Gynecology, College of Medicine and the Hospital of NTU from 1999 to 2005. Dr. Chow was the Principal Investigator of International HPV-008 Cervical Cancer Vaccine Trial (PATRICIA) during 2004-2010 at National Taiwan University Hospital, Taipei, Taiwan. Dr. Chow also obtained a patent from USA entitled “Tumor Marker for Ovarian Cancer Diagnosis” (Patent No. US 7,745,149 B2. June 29, 2010)

Abstract:

Despite the known fact that immunoglobulins are expressed among cancer cells, their roles in cancer immunology are still not fully understood. In 1987, a monoclonal antibody, RP215 was generated and later shown to recognize mainly a carbohydrateassociated (O-glycan) epitope located in the variable regions of heavy chain immunoglobulins (designated in general as CA215) expressed on the surface of cancer cells, but not those from normal B cells. Biological and immunological studies of cancerous immunoglobulins have been performed extensively with RP215 as the unique probe. Both anti-immunoglobulins and RP215 were shown to induce apoptosis and complementdependent cytotoxicity reactions to culturing cancer cells. In vivo nude mouse animal models also revealed dose-dependent reductions of implanted tumor upon injections of RP215. Gene regulation studies were performed by using semi-quantitative PCR with genes involved in immunoglobulins expressions and toll-like receptors. The binding of RP215 and antiimmunoglobulins to cancer cells was shown to affect similar levels of gene expressions with excellent mutual correlations (R2 ≥ 0.90). Human serum proteins which interact with affinitypurified CA215 and/or cancerous immunoglobulins were identified and found to consist of those with known pro-cancer or anti-cancer properties. These observations led to the hypothesis of dual functional roles of cancerous immunoglobulins in cancer cells. Interactions with relevant human serum proteins may be essential for proliferation/growth of cancer cells and may also be required to neutralize those hostile to cancer cells. In addition, RP215-based enzyme immunoassay kits are beneficial in monitoring serum levels of CA215 or cancerous immunoglobulins among cancer patients. Anti-cancer and pancancer nature of CA215 revealed that RP215 can be an ideal candidate for the development of anti-cancer drugs or therapeutic treatments. RP215-linked chimeric antigen receptor (CAR)-T cell therapy technology has been attempted for anti-cancer treatments, through a series of CAR construction and validations by cytotoxic cell killing and cytokine activity release assays. In conclusion, dual distinct functional roles of widespread cancerous immunoglobulins among cancer cells have been demonstrated for the potential applications of RP215 in therapeutic treatments of many human cancers.

Meetings International -  Conference Keynote Speaker Nick Kostovic photo

Nick Kostovic

Department of Energy, USA

Title: Cancer cured by bio electron's laser acupuncture

Biography:

From 1970 to 1997, after almost 30 years of research using all of his collective information, he developed K-BTE medical laser device, and discovered bio electrons and bio electron photons. He did it by my own funds in millions of US dollars /helped only by his family and his sister Snijezana Moller from Helsingborg in Sweden, and money he earned from different small businesses. He was able to realize his goal of creating a device to heal humanity. Using quantum mechanics in physics, biology and chemistry, in electromagnetic science and Chinese Acupuncture Science in Medicine making comparison with west US science in Medicine, he created his life's vision and destiny.

Abstract:

The K-BTE device simply releases bio electrons photons. Enriched by natural acids these bio electrons photons become capable of dissolving unhealthy particles in fiber tissue. Then dissolving and dispersing   unhealthy particles, it means number of sick particles, dead cells and oxidized proteins from fiber tissue without harm to the healthy cells. This dissolving and dispersing of extreme bad and dangerous unhealthy particles can operate in the brain or any other physical organ. In the brain, any kind of neurological disorders can be checked searching for deep painfully affected areas and then reversed by enriched bio electron photons. The same healing capability occurs identically in an atrophied muscle, bone and cartilage tissue. Also works for plaque in the entire vascular system by dispersing and healing.  The ever present keynote of the K-BTE device is always the lack of harm to healthy cells.

The K-BTE device attracts and transfers light of sun quanta particles consisting by its structure of element concentric rings which are consisted by bio-chemical charges of bio photons and electron neutrinos penetrating directly into the brain. This light injection fosters the regeneration, recovery and re-growth of neurons in the brain. This enlightening process facilitates the brain tissue to regain its ability to send impulses throughout the body while simultaneously improving mobility and homeostasis.

Meetings International -  Conference Keynote Speaker Gregory Lee photo

Gregory Lee

University of British Columbia, Canada

Title: Cancerous immunoglobulins and potential clinical applications

Biography:

Gregory Lee was professor at University of British Columbia in Vancouver, Canada until 2012. He received his PhD in physical biochemistry from California Institute of Technology Pasadena, CA in 1972. His major research interest is in the field of biotechnology. He has generated numerous monoclonal antibodies for immunodiagnostic and therapeutic applications, including the early pregnancy detection, ovulation, myocardial infarction and cancer. During the last decade, he has been focused on research and development of the monoclonal antibody-based anti-cancer drugs (noticeably RP215 and GHR106) for immunotherapy of human cancer. He has been serving as editors of several international journals related to cancer research since 2012.

Abstract:

Despite the known fact that immunoglobulins are expressed among cancer cells, their roles in cancer immunology are still not fully understood. In 1987, a monoclonal antibody, RP215 was generated and later shown to recognize mainly a carbohydrateassociated (O-glycan) epitope located in the variable regions of heavy chain immunoglobulins (designated in general as CA215) expressed on the surface of cancer cells, but not those from normal B cells. Biological and immunological studies of cancerous immunoglobulins have been performed extensively with RP215 as the unique probe. Both anti-immunoglobulins and RP215 were shown to induce apoptosis and complementdependent cytotoxicity reactions to culturing cancer cells. In vivo nude mouse animal models also revealed dose-dependent reductions of implanted tumor upon injections of RP215. Gene regulation studies were performed by using semi-quantitative PCR with genes involved in immunoglobulins expressions and toll-like receptors. The binding of RP215 and antiimmunoglobulins to cancer cells was shown to affect similar levels of gene expressions with excellent mutual correlations (R2 ≥ 0.90). Human serum proteins which interact with affinitypurified CA215 and/or cancerous immunoglobulins were identified and found to consist of those with known pro-cancer or anti-cancer properties. These observations led to the hypothesis of dual functional roles of cancerous immunoglobulins in cancer cells. Interactions with relevant human serum proteins may be essential for proliferation/growth of cancer cells and may also be required to neutralize those hostile to cancer cells. In addition, RP215-based enzyme immunoassay kits are beneficial in monitoring serum levels of CA215 or cancerous immunoglobulins among cancer patients. Anti-cancer and pancancer nature of CA215 revealed that RP215 can be an ideal candidate for the development of anti-cancer drugs or therapeutic treatments. RP215-linked chimeric antigen receptor (CAR)-T cell therapy technology has been attempted for anti-cancer treatments, through a series of CAR construction and validations by cytotoxic cell killing and cytokine activity release assays. In conclusion, dual distinct functional roles of widespread cancerous immunoglobulins among cancer cells have been demonstrated for the potential applications of RP215 in therapeutic treatments of many human cancers.

Meetings International -  Conference Keynote Speaker Nicola Maurea photo

Nicola Maurea

University of Kentucky, Italy

Title: LCZ 696 is superior to Valsartan in the prevention of cardiotoxity induced by trastuzumab, pertuzumab and Trastuzumab-DM1 monoclonal antibodies

Biography:

Nicola Maurea is the Chief of the Cardiology Department at the National Cancer Institute “IRCCS Fondazione Pascale” in Naples, Italy. He is one of the italian and international recognized leaders in the field of cardioncology and is President of the Italian Association of Cardioncology. He is Fellow of the European Society of Cardiology, American College of Cardiology and  National Association of Hospital Cardiologists (ANMCO). He is coauthor in numerous manuscripts on this topic in international journals and is regularly involved in national and international congresses and meetings as speaker or chairman.

Abstract:

Cardiotoxic effects related to anticancer drugs are among the leading causes of morbidity and mortality in cancer patients treated with Trastuzumab (T), Pertuzumab (P) and Trastuzumab-DM1 (TDM1) [1-3]. Sacubitril-valsartan (LCZ 696), a drug used for the treatment of heart failure in patients with a reduced ejection fraction, is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan.

In this study, we aim to assess whether LCZ 696, administered during T, P or TDM1 treatment, reduces in vitro anticancer drugs-related cardiotoxicity, more efficiently respect to Valsartan (V). We used our in Vitro model, the H9C2 rat cardiomyoblasts, treated with 200 nM of T, P or TDM1 for 3 days, and then treated in the absence or presence of 10 µM of LCZ 696 or V for additional 3 days.

Our results show that LCZ 696 is superior respect to V in the reduction of the cardiotoxic effects of T, P and TDM1, when administered to cultures of H9C2 cardiomyoblasts after antineoplastic treatments.

Indeed, LCZ 696 was significantly more effective than V in reducing T related cardiotoxicity, increasing cell viability of 25 % more, respect to V (p<0.001). LCZ 696 is more strong in the reduction of P related toxicity, increasing cell viability of 35% more respect to V, with p<0.001. And finally, again more effective than V in reducing TDM1 toxicity, increasing cell viability of 10 % (p<0, 05).

Keynote Session:

Meetings International -  Conference Keynote Speaker Nathalie Garcon photo

Nathalie Garcon

IRT BIOASTER, France

Title: Adjuvants and vaccines a millenium evolution

Biography:

Nathalie Garcon, PharmD, PhD, is currently the chief executive (CEO) and scientific officer (CSO) of BIOASTER. She joined BIOASTER, the French technology research institute for infectiology and microbiology as chief scientific officer in July 2014. She conducted two PhDs, worked at the Royal Free Hospital in London, then moved to the USA at Baylor College of Medicine in Houston, Texas, and joined SmithKline Beecham Biologicals now GlaxoSmithKline vaccines in 1990. She moved from this position, to head of technologies, head of research, vice president, head of global research and north America RD; and vice president, head of the global adjuvants and delivery systems centre for vaccines. In her last role within GSK vaccines before joining BIOASTER, Dr Garçon hold the position of vice president, head of adjuvants and technologies innovation centre. She provided leadership within GSK Biologicals in the fields of new vaccines technologies, from discovery to registration and commercialisation. Nathalie Garçon is Vice President and Head of Global Adjuvant and technologies innovation centre at GSK vaccines. Dr Garçon is the 2014 laureate of the Stanley Plotkin award for vaccines and vaccine technologies. She has authored over 60 papers and book chapters, is the editor of several books, and sits at the scientific committee of several journals. She holds more than 100 patents.

Abstract:

Since the first use of vaccination in the early 8th century to current time, vaccines have emerged as a biggest live saving intervention after clean water. Vaccines have followed an evolution following the evolution of technologies and scientific knowledge, and can be different in nature and purpose opening the door to their use not only to fight infectious diseases but also creating hope for the control and treatment of chronic disorders and cancer. Progresses in the understanding of the key role of the innate and adaptive immunity in the induction of protection to infection have had an impact on their design and the search for constant improvement of the efficacy and safety profile observed. Since the introduction of aluminium as the first adjuvant, several new adjuvants have been licensed in the context of various human vaccines. Their development has led to a new appreciation of the various steps to be undertaken to reach licensure, from research to licensure, including preclinical toxicology evaluation.The increased understanding of the innate and adaptive immune responses, host pathogen interactions, and the emergence of new and improved technologies over time, has shaped the way this was tackled, streamlined the necessary interaction required across the various bodies and expertise, providing a holistic approach to their development and licensure.This presentation will touch on the past, present and future of vaccines design.

Meetings International -  Conference Keynote Speaker Peter J Wookey photo

Peter J Wookey

University of Melbourne, Australia

Title: The expression, activity and targeting of calcitonin receptor, a putative tumour suppressor in the deadly brain tumour glioblastoma

Biography:

Peter Wookey completed his PhD from the Australian National University and postdoctoral studies at the University of Tübingen, Germany, supported by the Alexander von Humboldt Stiftung. He has spent many years in medical research at the University of Melbourne, where he manages a research group. He has developed antibodies that bind extracellular domains of GPCRs, conjugates for imaging programmed cell death and immunotoxins aimed at the treatment of glioblastoma. He has published more than 55 refereed manuscripts and filed patents granted in the US & EU with further patents pending. He is founder of two start-ups.

Abstract:

Calcitonin receptor (CTR) is highly expressed in the lethal brain tumour glioblastoma by glioma cells and glioma stem cells (1). Furthermore, evidence that CTR is a tumour suppressor in glioblastoma (2) is based on inactivating mutations that compromise the actions of an agonist. In view of the current consensus that glioma stem cells are highly invasive and provide resistance to conventional therapeutics, we investigated CTR as a potential therapeutic target on high grade glioma (HGG) cell lines that are similar to glioma stem cells. Pharmacological data from 4 HGG cell lines that express CTR show that 3 lines (JK2, PB1 & WK1) do not respond to calcitonin in contrast to SB2b, in which adenylyl cyclase is activated. Our group has developed monoclonal antibodies that (i) binds a specific epitope in the extracellular domain (ECD, mAb2C4), (ii) binds an epitope in the carboxyl terminus (mAb1H10) and (iii) that identifies the insert-positive isoform (mAb10G6). In contrast to the pharmacological inactivation, CTR protein was detected on immunoblots of cytosolic, nuclear and membrane fractions from the HGG cell lines with one exception, the membrane fraction from PB1. Immunotoxins (mAb2C4:dianthin and mAb2C4:gelonin) and an antibody:drug conjugate (ADC, mAb2C4:monomethyl auristatin E [MMAE]) were constructed and tested in HGG cell lines. When tested on JK2, SB2b and WK1, both immunotoxins were 250 times more potent than the ADC in the presence of the triterpene glycoside SO1861 that enhances endo-lysosomal escape (3). PB1, which expresses low levels of CTR in the membrane fraction, was resistant to the immunotoxins.

Meetings International -  Conference Keynote Speaker Francois M. Vallette photo

Francois M. Vallette

Universite de Nantes, France

Title: A tolerant-like population preceedes resistant cells to temozolomide in a glioma cell line

Biography:

Vallette has completed his PhD in 1984 from Paris VII University (France) and Postdoctoral Studies from The Department of Cell Biology of NYU School of Medicine (USA). He is the Director of Research INSERM, and leads a research group at the INSERM Unit 1232 (University of Nantes, France). He has published more than 130 papers in reputed journals and is serving as an editorial board member of several journals (BMC Cancer, Molecular Cancer, Oncogenesis)

Abstract:

Drug resistance affects the therapeutic efficacy in cancers and leads to tumour recurrence through ill-defined mechanisms. It is currently admitted that resistance can originate from specific sub-clones present at diagnosis, or acquired during the treatment through the transformation of cancer cells. Here, we use both mathematical and genomic approaches (a combination of transcriptomic and single cell analyses), to study the expression pattern during the expression of drug resistance in cancer. We use, as model, the human glioma cell line, U251, cultured in the presence of Temozolomide (TMZ), the chemotherapy standard of care for patients with glioblastoma (GBM) (1). We found that U251 cells become resistant to TMZ along with the induction expression of the DNA repair protein O6-methylguanine-DNA methyl-transferase (MGMT). However, prior to MGMT expression, TMZ induced a transient state wherein cells adopted a distinct morphology and expressed a specific set of genes. Epigenetics drugs were shown to specifically target this population and prevent the appearance of cells resistant to TMZ. Our results show that this transient population is essential for the development of resistant cancer cells and could constitute a therapeutic target in GBM. This population is reminiscent to tolerant populations described in response to tyrosine kinase inhibitor in other cancers.

Meetings International -  Conference Keynote Speaker Monjori Mitra photo

Monjori Mitra

Institute of Child Health, India

Title: Neglected infectious disease prevention - An Indian perspective, challenges and opportunities

Biography:

Monjori Mitra is an award winning pediatrician, academician, researcher, author, editor, clinical investigator and office bearer of Indian Academy of Pediatrics. She serves as associate professor of pediatric medicine in the esteemed Institute of Child Health, Kolkata. Her area of expertise is pediatrics vaccinology and nutrition. She carries a rich clinical experience of more than 20 years in pediatric medicine. She has served in the capacity of executive member of Indian Pediatric Society. She has been advisor to the editorial board of Indian Journal of Practical Pediatrics and Indian Pediatrics. She has been honorary speaker at various international and national conferences and forums. She has authored various articles, journals and books on vaccines, vaccinology, infectious diseases and rare pediatric diseases with various national and international publications in indexed journals. She has been the Principal investigator for a number of clinical trials conducted in pediatric population across several therapeutic areas.

Abstract:

Neglected diseases particularly infectious origin, needs  greater political commitment to combat these diseases, hence has been recognized by many World Health Assembly resolutions and the UN Millennium Development Goals. Diseases such as diarrheal diseases, malaria, chikunguniya, typhoid, tuberculosis, and neglected tropical diseases are rife where poverty prevails. According to data from the Global Burden of Disease Study 2010, the collective burden of neglected diseases is 248 million disability-adjusted life years (DALYs), and they caused 4 million deaths. Global immunization landscape is such that in the developing countries where 85% population lives and where the disease burden is 93%, the vaccine for these diseases are not developed. India loses close to 2 million lives a year due to vaccine preventable diseases. Vaccine coverage is also lowest in India.

It was in this backdrop the scientific community in India planned to address the diseases like typhoid, rotavirus diarrhea and many in the pipe lines and developed the vaccine in close association with scientific bodies of USA. Today few Indian companies have successfully developed vaccines at a much affordable cost and as per WHO requirement satisfied all the qualification to address the children of many underdeveloped countries’ vaccination coverage. Quality vaccines at affordable prices have been the key to success, an apt example, which are typhoid vaccines and rotavirus vaccines. Today globally the WHO and UNESCO in association with GAVI, CaT, TYVAC, has decided to vaccinate children with the highly efficacious conjugate typhoid vaccine in developing countries to combat multidrug resistant typhoid fever.

Meetings International -  Conference Keynote Speaker Monjori Mitra photo

Monjori Mitra

Institute of Child Health, India

Title: Neglected infectious disease prevention - An Indian perspective, challenges and opportunities

Biography:

Monjori Mitra is an award winning pediatrician, academician, researcher, author, editor, clinical investigator and office bearer of Indian Academy of Pediatrics. She serves as associate professor of pediatric medicine in the esteemed Institute of Child Health, Kolkata. Her area of expertise is pediatrics vaccinology and nutrition. She carries a rich clinical experience of more than 20 years in pediatric medicine. She has served in the capacity of executive member of Indian Pediatric Society. She has been advisor to the editorial board of Indian Journal of Practical Pediatrics and Indian Pediatrics. She has been honorary speaker at various international and national conferences and forums. She has authored various articles, journals and books on vaccines, vaccinology, infectious diseases and rare pediatric diseases with various national and international publications in indexed journals. She has been the Principal investigator for a number of clinical trials conducted in pediatric population across several therapeutic areas.

Abstract:

Neglected diseases particularly infectious origin, needs  greater political commitment to combat these diseases, hence has been recognized by many World Health Assembly resolutions and the UN Millennium Development Goals. Diseases such as diarrheal diseases, malaria, chikunguniya, typhoid, tuberculosis, and neglected tropical diseases are rife where poverty prevails. According to data from the Global Burden of Disease Study 2010, the collective burden of neglected diseases is 248 million disability-adjusted life years (DALYs), and they caused 4 million deaths. Global immunization landscape is such that in the developing countries where 85% population lives and where the disease burden is 93%, the vaccine for these diseases are not developed. India loses close to 2 million lives a year due to vaccine preventable diseases. Vaccine coverage is also lowest in India.

It was in this backdrop the scientific community in India planned to address the diseases like typhoid, rotavirus diarrhea and many in the pipe lines and developed the vaccine in close association with scientific bodies of USA. Today few Indian companies have successfully developed vaccines at a much affordable cost and as per WHO requirement satisfied all the qualification to address the children of many underdeveloped countries’ vaccination coverage. Quality vaccines at affordable prices have been the key to success, an apt example, which are typhoid vaccines and rotavirus vaccines. Today globally the WHO and UNESCO in association with GAVI, CaT, TYVAC, has decided to vaccinate children with the highly efficacious conjugate typhoid vaccine in developing countries to combat multidrug resistant typhoid fever.

Oral Session 1:

  • Trials in Vaccinology
Meetings International -  Conference Keynote Speaker Sarbjeet Sharma photo

Sarbjeet Sharma

Sri Guru Ram Das Institute of Medical Sciences and Research, India

Title: Vaccination in pregnancy

Biography:

Sarbjeet Sharma is a Clinical Microbiologist to the work of diagnostics for over 20 years, with keen focus on HIV and Tuberculosis. She has contributed many international and national publications and presentations, one of the latest being at ICAAC 2012, San Francisco, USA: “Comparative evaluation of Conventional techniques and Nested PCR in the diagnosis of Extra-pulmonary TB

Abstract:

Globally in general & in resource poor countries  like India in particular, immunization during pregnancy is a vital and cost-effective strategy that significantly reduces maternal illness and improves fetal outcomes besides imparting initial protection to the neonate against vaccine preventable diseases and associated complications. While routine inactivated vaccines, bacterial vaccines & toxoids are recommended   to   pregnant women, all live vaccines should be avoided because of a theoretical risk to the developing fetus. There is need for increased awareness among people& enhanced government initiative for widespread implementation of vaccination in pregnancy.