Session Introduction

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. 

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.

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.

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.

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.

Jin-Mei Lai

National Taiwan University, Taiwan

Title

TBA

Biography

Current Positions:

1. Now, Professor Emeritus, Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

Experiences:

1. Lecturer, School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
2. Associate Professor, School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
3. Professor, School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
4. Director, Health Science and Wellness Center, National Taiwan University, Taipei, Taiwan, ROC

Abstract

TBA

Title

TBA

Biography

Abstract

TBA

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).