Novel MOAs and targets for cancer drug development What s hot off the presses?
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1 Novel MOAs and targets for cancer drug development What s hot off the presses? Moderator: Jeremy Goldberg, President, JPG Healthcare LLC Panelists: Robert J Schneider, PhD, Associate Director, NYU Cancer Institute Director, Translational Cancer Research Co-director, Breast Cancer Research Program Paul B. Fisher, MPh, PhD, Professor and Chairman, Department of Human & Molecular Genetics, Founding Director, VCU Institute of Molecular Medicine, VCU School of Medicine, Thelma Newmeyer Corman Chair in Cancer Research, VCU Massey Cancer Center Carlo M. Croce, MD, The John W. Wolfe Chair in Human Cancer Genetics, The Ohio State University, Chairman, Dept. of Molecular Virology, Immunology and Medical Genetics, Director, Institute of Genetics Philip W. Kantoff, MD, Chief Clinical Research Officer, Chief, Division of Solid Tumor Oncology, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Professor of Medicine, Harvard Medical School
2 Impediments to Effective Systemic Oncolytic Viral Therapy of Cancer: A Fixable Problem? Inefficient transduction and lack of true cancer-specific targeting Viral replication alone does not work: bipartite viral approach (mda-7/il-24) Trapping of virus in the liver and immune clearance of the therapeutic ti virus Answer: Cancer Terminator Virus (CTV)
3 The PEG-3 Promoter Targets GFP Transgene Expression in Breast Cancers and Malignant Gliomas Breast Cancers Malignant Gliomas HMEC: Primary Human Breast Epithelial Cells PHFA: Primary Human Fetal Astrocytes
4 Cancer Terminator Viruses (M7-CTV): Conditional Viral Replication + Cancer- Selective Apoptosis, Immune Targeting PEG-PromProm E1A + E1B CMV-Prom mda-7/il-24 Conditionally Replication-Competent Adenovirus Normal Cells: No effect Primary and Distant Tumor Cells: Apoptosis, Immune Destruction
5 M7-CTV (mda-7/il-24) ) Cures Mice Containing Established Metastatic M12 Intraperitoneal Tumors Ad.vec Ad.PEG-E1A Ad.PEG-M7 M7-CTV (mda-7)
6 Tropism Modified Cancer Terminator Viruses (Ad.5/3-CTV) CTV): : An Improved CTV PEG-PromProm E1A + E1B CMV-Prom mda-7/il-24 Ad.5/3 Conditionally Replication-Competent Ad (Ad.5/3-CTV) Normal Cells: No effect Primary and Distant Tumor Cells: Apoptosis, Immune Destruction
7 Effect of Ad.5/3-CTV in Primary Human GBM6 Growing in Mouse Brains
8 Profound Therapeutic Activity of Ad.5/3-CTV in Primary GBM Grown in Mouse Brains
9 Breakthrough Treatment with Cancer Terminator Virus (CTV) Systemic Terminator Virus attacks distal tumors and cycle repeats Normal Cell Inject Terminator Virus -IV (Microbubble) -intra-tumoral t -intra-peritoneal Terminator Virus mda-7/il-24 Immune Response Oncolytic Cell Death & mda-7/il-24-stimulated Anti-Tumor Immune Response Cancer Cell
10 Ultrasound-Targeted Microbubble Delivery of CTV
11
12 Novel MOAs and targets for cancer drug development What s hot off the presses? Moderator: Jeremy Goldberg, President, JPG Healthcare LLC Panelists: Robert J Schneider, PhD, Associate Director, NYU Cancer Institute Director, Translational Cancer Research Co-director, Breast Cancer Research Program Paul B. Fisher, MPh, PhD, Professor and Chairman, Department of Human & Molecular Genetics, Founding Director, VCU Institute of Molecular Medicine, VCU School of Medicine, Thelma Newmeyer Corman Chair in Cancer Research, VCU Massey Cancer Center Carlo M. Croce, MD, The John W. Wolfe Chair in Human Cancer Genetics, The Ohio State University, Chairman, Dept. of Molecular Virology, Immunology and Medical Genetics, Director, Institute of Genetics Philip W. Kantoff, MD, Chief Clinical Research Officer, Chief, Division of Solid Tumor Oncology, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Professor of Medicine, Harvard Medical School
13 Novel MOAs and targets for cancer drug development What s hot off the presses? Discussion Points Dr. Philip Kantoff successes & challenges for new prostate cancer therapeutics androgen pathway inhibitors, bone targeting agents, Provenge immunotherapy Dr. Carlo Croce role of micro RNAs in Prognostic, Diagnostic, Therapeutic approaches to cancer Dr. Bob Schneider design of early clinical trials for mtor inhibitors, targeting protein synthesis and targeting oncogenic mrna Dr. Paul Fisher future of gene therapy in cancer therapeutic viruses, delivery, theranostics
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