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Immunotherapy target discovery remains one of the biggest challenges facing the field and, with the success of ipilimumab, researchers are being pushed to move forward at a rapid pace. Much work in this field is being done with agonist antibodies that target both T and B cells, modulating T cell activation and enhancing immune response. Cambridge Healthtech Institute's inaugural Agonist Immunotherapy Targets will showcase the in vivo and in vitro data that are providing a base for continued development of these therapies. Immune response to tumors, data on tumor necrosis factor receptors (TNFR), and potential challenges will also be discussed. Focus will also be given to potential combination immunotherapies to ensure durable antitumor response.

THURSDAY, MAY 7


Agonistic Receptors: Case Studies

12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

1:40 Chairperson’s Remarks

Andrew D. Weinberg, Ph.D., Chief, Laboratory of Basic Immunology, Providence Cancer Center

1:50 CDX-1127: An Agonist Antibody against CD27 for Safe and Specific Immune Activation

ThomasDavisThomas Davis, M.D., CMO, Clinical and Regulatory, Celldex Therapeutics

CDX-1127 has completed phase 1 and shown no toxicity and clear immunologic activation with objective tumor regressions. Preclinical data show marked synergy from multiple combinations with immune targeted agents. A range of combination studies are in progress.

2:20 Anti-Tumor Effects and Preclinical Development of the Human Agonistic CD40 Antibody ADC-1013

Peter Ellmark, Ph.D., Principal Scientist, Alligator Bioscience AB

Alligator Bioscience has developed a fully human agonistic CD40 antibody (IgG1), ADC-1013, optimized for tumor-directed immunotherapy by increasing potency and tumor retention. The design and anti-tumor effect in human CD40 transgenic mice using different syngeneic tumor models will be presented. Further, the toxicokinetics and pharmacodynamics markers identified in cynomolgus monkey will be discussed. To our knowledge, ADC-1013 represents the first CD40 antibody optimized for tumor directed immunotherapy of cancer, and it is currently in late preclinical development for clinical trials.

2:50 Pre-Clinical Evaluation of an Agonist Antibody Targeting ICOS

Jennifer MichaelsonJennifer S. Michaelson, Ph.D., Director, Research, Tumor Biology, Jounce Therapeutics

Jounce is developing an agonistic antibody to the co-stimulatory molecule ICOS. Preclinical studies demonstrate that anti-ICOS agonistic antibodies are efficacious in syngeneic tumor models, with enhanced efficacy observed in combination with PD-1 inhibition.

3:20 Hexavalent TNF-Receptor Ligands for Cancer Treatment and Immune Modulation: TRAIL, CD40L and Beyond

Tim Schnyder, Ph.D., Senior Scientist, Apogenix

3:50 Refreshment Break

4:20 Problem-Solving Breakout Discussions

Agonist Antibodies Targeting Checkpoint Proteins

Moderator: Robert Stein, M.D., Ph.D., CSO, Agenus

  • Stimulating anti-tumor response
  • Developing humanized mAbs as single agents or combinations
  • Combining agonists with anti-cancer vaccines

 

Combinations in Cancer Immunotherapy

Moderator: Andrew D. Weinberg, Ph.D., Chief, Laboratory of Basic Immunology, Providence Cancer Center

  • Agonists with Checkpoint inhibitors
  • Dosing and scheduling for combinations
  • Blocking suppressive cytokines in combination with Agonists and/or Checkpoint blockade
  • What are the cell types and mechanisms that different Agonists (OX40, CD40, CD27, 4-1BB etc...) affect and how does that compare to checkpoint blockade

5:20 End of Day

5:15 Registration for Dinner Short Courses

FRIDAY, MAY 8

8:00 am Morning Coffee


AGONIST RECEPTORS: CASE STUDIES (CONT.)

8:30 Chairperson’s Remarks

Thomas Davis, M.D., CMO, Clinical and Regulatory, Celldex Therapeutics

8:35 Targeted Costimulation with Novel Single-Chain 4-1BBL or OX40L Antibody-Fusion Proteins Promotes Tumor Directed T Cell Activation
Sina Fellermeier, Institut für Zellbiologie und Immunologie, Universität Stuttgart

9:05 Humanized Monoclonal Antibodies as Agonists for GITR or OX40 Signaling

Robert SteinRobert Stein, M.D., Ph.D., CSO, Agenus

We now know that there are many checkpoints in addition to CTLA-4 and PD-1. A new category of CPMs includes agonist antibodies targeting other checkpoint proteins, such as the receptors on T-lymphocytes called GITR and OX40. They stimulate anti-tumor immune responses and may play major roles in treating patients with a broad range of cancers. They can be developed as single agents and in optimized combinations, possibly including combinations with anti-cancer vaccines and other agents.

9:35 Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Anti-Tumor Effector / Memory CD8 T cells in a Poorly Immunogenic Tumor Model

Shihao Chen, Ph.D., Principal Scientist, Rinat Laboratories, Pfizer, Inc.

10:05 Coffee Break


Strategies for Combination Cancer Immunotherapy

10:35 OX40 Agonist Combined with PD-1 and TGFb Receptor Blockade

Andrew D. Weinberg, Ph.D., Chief, Laboratory of Basic Immunology, Providence Cancer Center

11:05 Enhanced Combination Immunotherapy Using Anti-PD-1 Antibodies and in Conjunction with Tumor Targeting Therapies

CaryOpelCary Opel, Graduate Researcher, Koch Institute, Massachusetts Institute of Technology

Cancer vaccine treatment, cytokine therapy, checkpoint blockade, and tumor-targeting antibody dosing allowed various immunological mechanisms to be activated in a syngenetic mouse model. The most aggressive combinations cured large, established, subcutaneous tumors without the need for adoptive cell transfer. Extensive characterization of the immune system response to the tumor created by the combination therapy revealed a complex interplay of various cell types to mount a durable rejection of the primary tumor, as well as subsequent rechallenge. Finally, cytokine therapy was shown to be essential for the enhancement of the other targeted therapies.

11:35 Improving Cancer Immunotherapy by Combining Costimulatory Agonists

 AdamAdlerAdam J. Adler, Ph.D., Professor, Immunology, University of Connecticut Health Center

Costimulatory receptor agonists can elicit T cell-mediated tumor immunity. Further, combining different agonists can enhance therapeutic impact. In particular, dual costimulation through CD134 plus CD137 elicits potent cytotoxic CD8+ T cells and, surprisingly, cytotoxic CD4 Th1 cells. In addition to directly targeting tumors, these cytotoxic CD4 Th1 cells appear to maximize the overall anti-tumor T cell response by providing both antigen-linked and non-linked help.

12:05 pm Attend Concurrent Session

12:35 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own

1:05 Refreshment Break


Overcoming Challenges with the TNF Super Family/Immunomodulators

1:35 Chairperson’s Remarks

Denise L. Faustman, M.D., Ph.D. Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School

1:40 IL-12: A Safe Bet for Combination Immunotherapy

ChrisLawrenceChris Lawrence, Ph.D., Senior Director, Research, Neumedicines Inc.

We have safely advanced HemaMax™, a subcutaneously administered recombinant human IL-12, to Phase 1B clinical trials and have developed a new clinical paradigm for its combined use with either chemotherapy, radiotherapy or immunotherapy. We present evidence that HemaMax is expected to provide a durable anti-tumor response through immunoactivation, and anti-angiogenic effects in various cancer types, while mitigating blood toxicity, and is safe, well tolerated and non-immunogenic.

2:10 Using the TNF Superfamily Ligands (TNFSF) as Many-Trimer Multimers for Vaccines and Cancer Immunotherapy

RichardKornbluthRichard S. Kornbluth, M.D., Ph.D., President & CSO, Multimeric Biotherapeutics, Inc.

TNF superfamily ligands (TNFSF) are trimeric, Type II membrane proteins that can be released from the cell surface by proteolysis as soluble trimeric proteins. While the soluble trimer of TNF itself has some activities, most TNFSFs act by clustering their respective receptors on responding cells, which necessitates a multi-trimer arrangement for the TNFSF ligands. To mimic the natural cell surface array of TNFSFs, we have developed fusion proteins consisting of TNFSF extracellular domains joined to self-assembling multimerizing scaffolds based on Acrp30 or surfactant protein D (SPD). The resulting 2- and 4-trimer soluble TNFSFs have high activity both in vitro and in vivo. Four immunologically active, multi-trimer TNFSFs will be highlighted: CD40L, 4-1BBL, OX40L, and GITRL.

Unpublished Data

2:40 Suppression of Human Regulatory T Cells for Oncology Indications Using TNFR2 Antagonism

DeniseFaustmanDenise L. Faustman, M.D., Ph.D., Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School

Human regulatory T cells (Tregs) are a subpopulation of T lymphocytes that play a critical role in regulation of the immune response. In cancer, these cells are considered the greatest barrier to successful immunotherapy because of their ability to powerfully inhibit the body’s antitumor immune response when recruited or induced by growing tumors. Selective Treg inactivation using a TNFR2 antagonist antibodies has enabled the development of new therapeutic regimens for oncology indications. Major near-term market opportunities in cancer include both hematologic and non-hematologic malignancies.

3:10 PANEL DISCUSSION: EMERGING IMMUNOTHERAPY TARGETS

DeniseFaustmanModerator: Denise L. Faustman, M.D., Ph.D., Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School

Panelists to be Announced




4:10 End of Conference

 


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