2015 Archived Content

Cambridge Healthtech Institute’s 3rd Annual
Immunomodulatory Therapeutic Antibodies for Cancer
The Evolution of the PD-1 Axis, Emerging Immunotherapy Targets and Indications, Developing Multifunctional Antibody Immunotherapies
August 24-25

Recent regulatory approvals and a succession of favorable clinical data from the checkpoint inhibitor programs of major pharmas are now spearheading a new focus on immune system-modulating antibody therapeutics.  These results are now driving interest across academic and industry research into a next generation of checkpoint blockades and co-stimulatory factors, and the application of these to additional tumor types and in exciting new roles in combination treatment regimens.  For 2015, CHI’s Third Annual Immunomodulatory Therapeutic Antibodies for Cancer will explore developments in mainstream and emerging targets in this space, review progress in the application of immunotherapy for difficult to treat cancers and consider different concepts for developing multifunctional antibody immunotherapies.

Then, with this meeting as a foundation, the following ImVacS conference, Rational Combination Cancer Immunotherapy, will review strategies for combining immune-modulating antibodies with traditional and experimental therapeutics for improved clinical benefit to patients.

Day 1 | Day 2 | Download Brochure | Speaker Biographies 
UD: Unpublished Data | CS: Case Study

Recommended Dinner Short Course*
Targeting the Cancer Mutanome
*Separate registration required


7:15 am Registration & Morning Coffee


8:10 Chairperson’s Opening Remarks

Tariq GhayurTariq Ghayur, Ph.D., Distinguished Research Fellow, AbbVie Bioresearch Center


Michael B. Atkins, M.D., Deputy Director, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center


Kurt Schalper
9:00 Current Insights on the PD-1/PD-L1 Axis as a Therapeutic Target in Oncology: A Biomarker Perspective

Kurt Schalper, M.D., Ph.D., Associate Research Scientist, Pathology, Yale University School of Medicine

Monoclonal antibodies targeting the co-inhibitory immune checkpoint PD-1 or its primary ligand PD-L1 are well tolerated and can induce lasting clinical responses in patients with advanced malignancies. However, the majority of patients treated with such agents do not receive clear benefit, highlighting the need for companion biomarkers to select subjects with the highest potential of benefit. Current status and recent developments in biomarkers for PD-1/PD-L1 axis therapies will be discussed.

9:30 Coffee Break

10:00 Intellectual Property Review of Major Immunotherapy Targets: Non Composition of Matter Approaches to Developing Unique IP in Cancer Immunotherapy

Konstantin M. LinnikKonstantin M. Linnik, Ph.D., Partner, Intellectual Property, Nutter, McClennen & Fish, LLP

Immunoncology IP is crowded – the number of drugs in R&D far exceeds the number of targets. Navigating the IP around major targets is critical but, more importantly, every drug developer faces challenges in protecting its own intellectual property. What are the patenting approaches that allow entry into this crowded IP space, while preserving the broadest scope of protection?


10:30 New and Noteworthy Solid Tumor Indications for Checkpoint Inhibitors

Amit MahipalAmit Mahipal, M.D., Medical Director, Clinical Research Unit; Assistant Member, H. Lee Moffitt Cancer Center & Research Institute

Immune checkpoint inhibitors have demonstrated high response rates and prolonged survival in selected tumor types and have been approved for treatment of melanoma. Checkpoint inhibitors are currently being evaluated in phase III trials for treatment of non small cell lung cancer, renal cell carcinoma and other cancers. Remarkable response rates and durable responses are also seen in other tumors including bladder cancer, gastric cancer and head and neck cancers that would be focus of this talk.

Güllü Topal Görgün
11:00 Targeting Immune Suppressive Microenvironment by Immune Checkpoint Blockade in Multiple Myeloma

Güllü Topal Görgün, Ph.D., Senior Research Scientist, Dana-Farber Cancer Institute

PD1/PD-L1-signaling promotes tumor growth while inhibiting anti-tumor immune responses. Here we assessed the impact of single and dual blockade of PD1/PD-L1, alone or in combination with lenalidomide, on accessory and immune cell function as well as multiple myeloma (MM) cell growth in the immune suppressive BM milieu. We demonstrated that checkpoint signaling plays an important role in providing the tumor-promoting, immune-suppressive microenvironment in MM, and that blockade of PD1/PD-L1-signaling induces anti-MM immune responses that can be enhanced by lenalidomide.

11:30 Sponsored Presentation (Opportunity Available)

12:00 pm Luncheon Presentation: Breaking Down the Barriers to Immune Infiltration in the Tumor Microenvironment by Neutralization of Semaphorin 4D

Evans_ElizabethElizabeth Evans, Ph.D., Director, Oncology Research, Vaccinex Inc.

The tumor stroma creates an immunosuppressive microenvironment that restricts immune-mediated tumor rejection.  Semaphorin 4D represents a novel target with a unique mechanism for immunomodulation.  SEMA4D is highly expressed at the invasive tumor margin and acts as a guidance molecule, restricting movement of tumoricidal immune cells into the TME.  Antibody neutralization of the SEMA4D barrier enhances penetration of activated monocytes and T cells that serves to inhibit syngeneic tumor growth and can enhance activity of other immunomodulatory therapies.


1:25 Chairperson’s Remarks

Paul D. RennertPaul D. Rennert, Founder & Principal, SugarCone Biotech Consultants LLC

1:30 Tumor Associated Macrophages and CD4 T Cells Have Non-redundant Roles in the Suppression of CD8 T Cell Infiltration into Melanoma

Susan KaechSusan Kaech, Ph.D., Associate Professor, Immunobiology, Yale University School of Medicine

In melanoma patients, ~60% of patients have Braf-V600E mutation and Braf-V600E selective inhibitor, PLX4720, has been shown to trigger melanoma regression. We analyzed the composition and activities of tumor-infiltrating immune cells in an inducible melanoma model based on Cre-mediated Braf-V600E activation and Pten inactivation. Our results suggest that modulation of Braf activity in tumors and possibly also immune cells promotes anti-tumor immune responses and reveals the importance of CD40L-CD40 interaction in PLX4720-mediated antitumor response.

2:00 Building a Robust Translational Sciences Platform for Tumor Immunotherapy: From Identification of New Targets to Patient Enrichment Strategies

Sriram SathySriram Sathy, Ph.D., Director, Translational Sciences, Jounce Therapeutics

Jounce is focused on developing cancer immunotherapies that are geared to provide durable clinical responses through identification of optimal targets for specific indications and for certain subsets, patients within those indications. Towards this goal we have developed a robust translational platform that allows for both target identification as well as patient/indication selection in an unbiased fashion. This approach relies on the fundamental principle of defining the immune system content and characteristics via a comprehensive multiple parameters approach.

Andrea Facciabene
2:30 Local Endothelial Complement Activation Reverses Endothelial Anergy and Enables Effective T Cell Tumor Infiltration and Immunotherapy

Andrea Facciabene, Ph.D., Research Assistant Professor, Obstetrics and Gynecology, University of Pennsylvania School of Medicine

Cancer immune therapy depends on the ability of T cells to infiltrate tumors through the tumor endothelium. We demonstrated tumor infiltration by antitumor T cells in vivo requires local endothelial complement activation and anaphylatoxin release. Th1 cytokines, released by tumor-reactive T cells, induce endothelial C3 expression, local complement activation, and C5a anaphylatoxin release. This promotes the upregulation of ICAM-1 and VCAM-1 and T cell adhesion to the endothelium, circumventing the endothelial barrier in vivo and in vitro.

3:00 Refreshment Break

Weiming Yuan
3:30 Anti-Tumor Function of an Anti-iNKT TCR Monoclonal Antibody

Weiming Yuan, Ph.D., Assistant Professor, Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California

Invariant natural killer T (iNKT) cells are potent anti-tumor T cells. Anti-tumor clinical trials using the iNKT cell ligand, α-galactosylceramide (α-GalCer) have had limited success and one major limitation of α-GalCer-based therapies is the bioavailability of lipid drugs. We have engineered a murine iNKT TCR-targeting monoclonal antibody (NKT14m) and investigated its in-vivo anti-tumor function. We detected a synergistic anti-tumor function of the NKT14m antibody when administered in combination with IL-12.

Laszlo Radvanyi
4:00 The Next Generation of TIL Therapy using Immune Modulator Combinations

Laszlo Radvanyi, Ph.D., CSO, Lion Biotechnologies

The use of autologous tumor-infiltrating lymphocytes (TIL) has made significant advances recently, with commercial efforts underway towards regulatory approval as a potent cell therapy for melanoma and other solid tumors.  I will discuss progress towards this goal, including development of biomarkers for patient selection, optimized cytokine therapy after TIL infusion, approaches to improve TIL manufacturing methods, and current efforts to combine TIL therapy with immunomodulators such as T-cell checkpoint blockade.

Paul D. Rennert
4:30 Immunomodulatory Antibody Targets in the Tumor Microenvironment

Paul D. Rennert, Founder & Principal, SugarCone Biotech Consultants LLC

CTLA-4 and PD-1/PD-L1 antagonists target T cell immune checkpoint pathways. Novel immune modulatory targets have been identified in the Immunoglobulin superfamily, the TNFR superfamily, and on NK and other cells. Moreover, many inhibitory factors are expressed by or secreted by myeloid and stromal cells within the tumor microenvironment: it is here that we find critical metabolic, growth factor and chemokine receptor targets that control immunosuppression and are important therapeutic targets.

5:00 End of Day

Day 1 | Day 2 | Download Brochure | Speaker Biographies 
UD: Unpublished Data | CS: Case Study


7:25 am Morning Coffee


7:55 Chairperson’s Opening Remarks

John Haurum, M.D., D.Phil., CEO, F-star GmbH & F-star Biotechnology Ltd.

Tariq Ghayur
8:00 Design and Construction of Tri- and Tetra-Specific Ig Molecules to Regulate T Cell Functions and Immune Responses

Tariq Ghayur, Ph.D., Distinguished Research Fellow, AbbVie Bioresearch Center

Four dual-variable-domain – Ig (DVD-Ig™) molecules are in clinical development for autoimmune and oncology indications. Now we have extended the DVD-Ig concept to design & construct tri- and tetra-specific (multi-specific) molecules to address additional unmet needs. In this presentation we will describe: (1) some basic functional and stability features of these molecules and; (2) how these molecules can be used to fine tune T cell functions within the context of re-directed toxicity against tumor cells.

Charles L. Sentman
8:30 Multivalent Antibody Therapeutics for Cancer Immunotherapy

Charles L. Sentman, Ph.D., Professor, Microbiology and Immunology; Director, Center for Synthetic Immunity, Geisel School of Medicine, Dartmouth College

Natural killer (NK) cells have the ability to recognize a wide variety of tumor types. We have developed a series of bispecific antibody-like proteins based on NK cell receptor recognition for use in cancer immunotherapy. This presentation will describe the potential of these novel reagents to treat cancer and promote host anti-tumor immunity.

9:00 Immunomodulatory Bispecific Antibodies

Barbara SwansonBarbara Swanson, Ph.D., Director, Research, Sorrento Therapeutics, Inc.

Using chemical and molecular biology techniques, Sorrento has developed new approaches to generate bispecific antibodies (BsAbs). Both the chemical method, involving specific hetero-dimerization of two half antibodies using bio-orthogonal chemistry, and the molecular biology approach will be discussed. BsAbs utilizing an immunomodulatory antibody paired with a second antibody targeting cancer-associated antigens have been produced, and results from the biochemical and biophysical characterization and cell-based functional assays will be presented.

9:30 ARGX-115, A Monoclonal Antibody Against GARP/TGF-β1 Complexes Inhibits the Immunosuppressive Activity of Human Regulatory T Cells In Vivo

Michael Saunders, Ph.D., Senior Director Targets and Programs, arGEN-X, Belgium

GARP is a membrane receptor protein expressed on activated Treg cells that binds latent TGF-beta-1 and is required its activation. Two antibodies against GARP inhibit active TGF-beta-1 production and inhibit Treg suppressive activity in vitro. In a xenogeneic graft-versus-host disease model implanting human PBMCs into immunocompromised mice, these antibodies inhibit the immune suppressive function of human Tregs. GARP may represent a novel immunotherapeutic target for the treatment of cancer or chronic infections.

10:00 In vivo Efficacy of a Bispecific Molecule Targeting CTLA-4 and EGFR

Jacqueline DoodyJacqueline Doody, Vice President, Immunology, F-star Biotechnology Ltd.

A bispecific antibody was generated by engineering the constant region against EGFR and combining with the variable domain of CTLA-4. The ensuing EGFR/CTLA-4 bispecific showed efficacy in an in vivo model compared to either EGFR or CTLA-4 alone. Efficacy of the bispecific in the mouse model did not correlate with Treg depletion, suggestive of a novel biology.

10:15 Sponsored Presentation (Opportunity Available)

10:30 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

Polly-Matzinger11:15 PLENARY KEYNOTE Dangerous Thoughts on Immunotherapy

Polly C. Matzinger, Ph.D. Senior Investigator, Ghost Lab, Laboratory of Immunogenetics, NAID/NIH

What we think influences what we do. If we continue to view the immune system through the old fashioned self-non-self model, the likelihood of finding truly effective immunotherapies is vanishingly small, whether those therapies are for autoimmunity, cancer or transplantation. I will delineate the different predictions from the various models of immunity and show how they influence how we approach immunotherapy.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Close of Immunomodulatory Therapeutic Antibodies for Cancer

Day 1 | Day 2 | Download Brochure | Speaker Biographies

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