Cytokine-Based Immunotherapies

Cytokine-Based Immunotherapies

Tuesday, April 7, 2015

The New York Academy of Sciences

Presented By

 

Cytokines are small, short-lived proteins produced by a broad range of cells that play an important role in health and disease, specifically in host responses to infection, inflammation, trauma, sepsis, cancer, and reproduction. Preclinical studies have shown that many cytokines have considerable clinical potential as antiviral and anticancer agents or to suppress inflammatory and autoimmune conditions. However, in the clinic substantial systemic toxicity associated with cytokine dosing regimens prevents escalation to therapeutically active regimens. One strategy to circumvent this toxicity problem is the development of immunocytokines: cytokines fused to a binding module such as a scFv-antibody fragment or a nanobody to target them to selected cells and/or sites of disease. Targeted delivery of immune-stimulatory or immune-regulatory cytokines represents a promising strategy for the treatment of cancer and chronic inflammatory diseases, respectively, by improving the therapeutic index with acceptable side effects. As of 2012 there were over 40 immunocytokines tested in animal models which assessed biodistribution properties and/or therapeutic performance; nine of these entered clinical development. Although the use of antibodies as the delivery vehicle has improved the therapeutic index of cytokines, additional efforts are still being explored. One such effort; "activity-by-targeting", utilizes mutated cytokines that alter receptor binding properties combined with selective targeting to cells or tissues.

*Reception to follow.

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Agenda

* Presentation titles and times are subject to change.


April 7, 2015

8:30 AM

Registration and Continental Breakfast

9:00 AM

Introductory Remarks
Sonya Dougal, PhD, New York Academy of Sciences
Scott Brodeur, PhD, Bristol-Myers Squibb

9:15 AM

Keynote Address
Interleukin-2 (IL-2) as Treatment for Renal Cell Carcinoma and Melanoma
Dr. James Mier, MD, Beth Israel Deaconess Medical Center, Harvard Medical School

9:55 AM

Theoretical and Experimental Analysis of Immunocytokine Biodistribution at the Cellular Level
K. Dane Wittrup, PhD, Massachusetts Institute of Technology

10:35 AM

Networking Coffee Break

11:05 AM

Re-Configuring Immunocytokines to Increase Tumor Targeting of Neuroblastoma and Melanoma while Greatly Reducing Potential Toxicity
Stephen Gillies, PhD, Provenance Biopharmaceuticals Corp.

11:45 AM

Anti-Tumor Activity and Immune Mechanisms of the NHS-IL12 Immunocytokine
Robert Tighe, PhD, EMD Serono

12:25 PM

Networking Lunch Break

1:40 PM

Armored CAR T Cells: Utilizing Cytokines and Proinflammatory Ligands to Enhance CAR T Cell Anti-Tumor Efficacy
Renier J. Brentjens, MD, PhD, Memorial Sloan Kettering Cancer Center

2:20 PM

Restoration of Regulatory T cell Homeostasis with Low Dose IL2 Therapy in Patients with Graft versus Host Disease
Jerome Ritz, MD, Harvard Medical School

3:00 PM

Networking Coffee Break

3:30 PM

High Efficiency Targeting of Interferon Alpha Activity
Gilles Uzé, PhD, Montpellier University

4:10 PM

Panel Discussion

5:00 PM

Closing Remarks
Kerry Ralph, MS, Boehringer Ingelheim Pharmaceuticals Inc.

5:05 PM

Networking Reception

6:00 PM

Adjourn

Speakers

Organizers

Scott Brodeur, PhD

Bristol-Myers Squibb

Scott MacDonnell, PhD

Boehringer Ingelheim Pharmaceuticals Inc.

Kerry Ralph, MS

Boehringer Ingelheim Pharmaceuticals Inc.

Sonya Dougal, PhD

The New York Academy of Sciences

Keynote Speaker

James W. Mier, MD

Beth Israel Deaconess Medical Center/ Harvard Medical School, Boston, MA

James W. Mier, MD is an Associate Professor of Medicine at the Beth Israel Deaconess Medical Center, one of the teaching hospitals of Harvard Medical Center and one of the institutions comprising the Dana Farber Harvard Cancer Center. He received his oncology training at the National Cancer Institute and his research training in the Laboratory of Tumor Cell Biology under the direction of Dr. Robert Gallo. While at the NCI, he was involved in the isolation and characterization T-cell growth factor (IL-2). He subsequently was involved in the clinical testing of IL-2 that led to its FDA approval for patients with renal cell carcinoma (RCC) or melanoma. His early laboratory work was focused on the mechanisms underlying the fever, hypotension and other side effects induced by IL-2 treatment and he was the first to demonstrate that IL-2 is a potent inducer of other cytokines such as IL-1 and TNF. These inducible pyrogenic cytokines were shown to mediate the fever, hepatic acute phase response, neutrophil chemotactic defect, and other effects induced by IL-2 treatment. With the advent of targeted therapies for RCC, he has shifted his laboratory focus to explore the mechanisms by which RCC escape from VEGF-targeted drugs.

Speakers

Renier J. Brentjens, MD, PhD

Memorial Sloan Kettering Cancer Center

Dr Brentjens obtained an MD/PhD (microbiology) from SUNY Buffalo, completed residency in medicine at Yale New Haven Hospital, and a medical oncology fellowship at Memorial Sloan Kettering Cancer Center (MSKCC). Currently, Dr Brentjens is an associate member on the faculty at MSKCC and an attending physician on the leukemia service. As a medical oncology fellow during his training at MSKCC, Dr Brentjens initiated the initial pre-clinical studies demonstrating the potential clinical application of autologous T cells genetically modified to target the CD19 antigen through the retroviral gene transfer of artificial T cell receptors termed chimeric antigen receptors (CARs). Following completion of his medical oncology training, Dr Brentjens became the principle investigator of his own laboratory. As a PI, Dr Brentjens successfully translated these studies to the clinical setting treating patients with relapsed CD19+ tumors including chronic lymphocytic leukemia (CLL) and B cell acute lymphoblastic leukemia (B-ALL). Ongoing pre-clinical research in the laboratory is focused on the further development of CAR modified T cells designed to overcome the hostile immunosuppressive tumor microenvironment through the generation of “armored CAR T cells” currently being translated to the clinical setting as second generation CAR modified T cell clinical trials. Additionally, work in the Brentjens' lab has expanded this CAR technology to target additional tumor antigens expressed on other tumors including targeting the MUC-16 antigen expressed on ovarian carcinomas as well as the more ubiquitous WT-1 tumor associated antigen. These latter projects are similarly in the process of translation to the clinical setting.

Stephen D. Gillies, PhD

Provenance Biopharmaceuticals, Carlisle, MA

Dr. Gillies is an expert in the creation and development of recombinant antibodies and immunotherapies. Prior to founding Provenance Biopharmaceuticals Corp, Dr. Gillies led all scientific and business endeavors of Lexigen Pharmaceuticals Corp After Lexigen’s acquisition in 1999 by Merck KGaA, Dr Gillies had the additional responsibility of overseeing Global Oncology Pre-clinical research. Previously, he was Vice President of research at Damon Biotech and Abbott Biotech Inc., where he oversaw development of recombinant antibodies and pro-urokinase, an anti-clotting protein. As a postdoctoral fellow at the Massachusetts Institute of Technology, he identified the first cellular enhancer sequences that were found to be critical for the regulation of antibody expression. This discovery proved a key part of the commercial success of Erbitux, a cancer drug marketed by Imclone Systems Inc., Bristol Myers Squibb, and Merck KGaA. As part of his recombinant antibody project work, Dr. Gillies invented and implemented the immunocytokine technology, and leveraged through his academic network, the first proof of principle of this approach.  Dr. Gillies received his MS degree and PhD in Microbiology from the College of Medicine and Dentistry, Rutgers University and his BS degree in Microbiology from the University of Massachusetts, Amherst.

Jerome Ritz, MD

Harvard Medical School

Dr. Ritz is currently Professor of Medicine at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital and Harvard Medical School. He is Executive Director of the Connell-O'Reilly Cell Manipulation Core Facility (CMCF). The CMCF is a GMP processing facility that provides manufactured cellular products of various types for patients enrolled on clinical trials evaluating novel cellular therapies for cancer and other diseases. These include cellular cancer vaccines, immune cells for adoptive cell therapy and genetically modified cells. Dr. Ritz has been a successful laboratory and translational scientist for over 35 years. His major interests have been in cancer immunology and hematopoietic stem cell transplantation. Recent studies in his laboratory have focused on immune reconstitution in patients undergoing hematopoietic stem cell transplantation.  In this setting, donor immune cells play a critical role in the recognition and elimination of residual leukemia cells (graft versus leukemia – GVL) but immunologic targeting of normal recipient cells also leads to GVHD and damage to normal tissues. Studies of immune reconstitution have demonstrated that donor B cells and regulatory T cells play important roles in the development of GVL and GVHD. These observations have led to the development of new strategies to selectively modulate immune reconstitution to improve patient outcomes after transplant.

Robert Tighe, PhD

EMD Serono

Mr. Tighe is currently the Associate Director of ImmunoPharmacology in the Immuno-Oncology Translational Innovation Platform at EMD Serono, where has been an employee for over 10 years. His research team has characterized the in vivo efficacy and immune mechanism for a wide variety of immunomodulatory cancer therapies including immunocytokines, cancer vaccines, checkpoint inhibitor antibodies, and novel fusion proteins. He has made major contributions to several successful IND filings within the EMD Serono immuno-oncology pipeline, including the NHS-IL12 immunocytokine and the anti-PD-L1 antibody, avelumab.  Prior to transitioning into industry, Mr. Tighe conducted academic research on the MIT campus for over six years where he worked in the laboratories of world leading researchers including Bob Weinberg.

Gilles Uzé, PhD

Université Montpellier II, Montpellier, France

Gilles Uzé was trained in the Laboratory of Ion Gresser (Villejuif, France) and received his PhD in 1986 from the University of Paris VII. After having cloned the interferon receptor, he moved in 1993 to Montpellier (France) where he is currently Research Director at the Centre National de la Recherche Scientifique (CNRS). He has a long-term experience in the study of structure-function relationship of IFN and receptor components and he has contributed to the understanding of the biological significance of the multiple type I IFN subtypes.

K. Dane Wittrup, PhD

Massachusetts Institute of Technology, Cambridge, MA

Professor K. Dane Wittrup is the Carbon P. Dubbs Professor of Chemical Engineering and Biological Engineering at the Massachusetts Institute of Technology, and the Associate Director of the Koch Institute for Integrative Cancer Research. Prof. Wittrup received a BS in Chemical Engineering Summa cum Laude in 1984 from the University of New Mexico, and a PhD in Chemical Engineering from the California Institute of Technology in 1988 under the thesis direction of Prof James Bailey. Wittrup’s research program is focused on protein engineering of biopharmaceutical proteins by directed evolution. Areas of interest include: pretargeted radioimmunotherapy; biological response modification of EGFR; and immunotherapy of cancer via engineered cytokines and vaccines.

Sponsors

For sponsorship opportunities please contact Perri Wisotsky at pwisotsky@nyas.org or 212.298.8642.

Exhibitor

Precision Antibody

Promotional Partners

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Mary Ann Liebert, Inc., publishers

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The Biochemical Pharmacology Discussion Group is proudly supported by

  • Merck
  • WilmerHale

Mission Partner support for the Frontiers of Science program provided by Pfizer

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