Using lessons learned from early cancer vaccines and immunotherapeutics, a new wave of programs are underway that promise improved efficacy and safety over a wider range of cancers. Emerging Cancer Immunotherapies and Vaccines will examine new targets and strategies in this space, along with important studies in preclinical development associated with developing these programs into successful drug products. Speakers will offer approaches to resolve the most challenging steps in the transition of these programs from research into clinical development.

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TUESDAY, AUGUST 13, 2013

7:30 am Main Conference Registration and Morning Coffee

8:05 Chairperson’s Opening Remarks

Adam J. Adler, Ph.D., Associate Professor of Immunology, University of Connecticut

T Cell Immunotherapy Strategies 

9:00 It Takes Two to Tango: Fine Tuning of Tumor Cells and T Lymphocytes for Maximized Anti-Tumor Activity

Daniel J. Powell, Jr., M.D., Assistant Professor, Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

Genetic engineering with chimeric immune receptors now allows for rapid de novo generation of autologous T cells with potent anti-tumor activity for adoptive cell transfer therapy for cancer. Still, low target antigen expression by tumor cells and antigen expression on normal tissues may render therapy ineffective or potentially toxic. We have identified agents that sensitize tumor cells to immune attack and made advances in T cell engineering strategies to better direct T cells to tumor antigen and confine T cell activity to tumor.

9:30 Improved Cancer Immunotherapy through CD134 plus CD137 Dual Co-Stimulation

Adam J. Adler, Ph.D., Associate Professor of Immunology, University of Connecticut

T cell-mediated anti-tumor immunity is dampened by tolerance mechanisms that evolved to prevent autoimmunity. Since tolerance largely results as a consequence of insufficient co-stimulation during antigenic priming, co-stimulatory receptor agonists can program tumor-specific T cell expansion and effector differentiation. In particular, dual administration of agonists to CD134 plus CD137 activates multiple immune cells with tumoricidal potential including NK cells, cytotoxic CD8+ T cells, and surprisingly, cytotoxic CD4+ T cells.

10:00 Refreshment Break

Cancer Biology and Biomarkers 

10:30 Vascular Normalization as an Emerging Strategy to Enhance Cancer Immunotherapy

Rakesh K. Jain, Ph.D., Andrew Werk Cook Professor of Tumor Biology, Harvard Medical School; Director, E.L. Steele Laboratory of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital

The immunosuppressive tumor microenvironment remains a limiting factor for anti-cancer vaccine therapies. In addition, tumors systemically alter immune cells’ function via secretion of cytokines such as VEGF, a major pro-angiogenic cytokine. Hence, anti-angiogenic treatment may be an effective modality to potentiate immunotherapy. I will discuss the effects of VEGF on anti-tumor immune responses, and propose a potentially translatable strategy to re-engineer the tumor immune microenvironment and improve cancer immunotherapy.

11:00 Advances in Biomarker Validation and Trial Design for Antitumor Immunotherapy

Susan R. Slovin, M.D., Ph.D., Genitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan–Kettering Cancer Center

Conventional imaging modalities have been the mainstay of assessing treatment response. Recent data suggests that evaluating circulating tumor cells may provide insight regarding changes in the tumor cells’ overall behavior. Immunologic treatments often do not impact the cancer with immediacy; a means of determining whether an immunologic target is hit and whether it impacts the tumor’s biology remains a challenge. Changes in T cell populations or myeloid suppressor cells may reflect potential impact on the intra- and extra-tumoral milieu.

11:30 Exploring Synergy between Targeted Therapy and Immunotherapy

Zachary Cooper, Ph.D., Postdoctoral Research Associate, Surgical Oncology, Massachusetts General Hospital

Recent advances in the treatment of melanoma include the use of BRAF-targeted therapy and immune checkpoint inhibitors, though each of these treatments alone has its limitation. There is increasing evidence for synergy between these modalities. Treatment with a BRAF inhibitor results in enhanced melanoma antigen expression and a more favorable microenvironment. Exploring the potential synergy using mouse models is necessary in overcoming monotherapy limitations.

12:00pm Sponsored Presentations (Opportunities Available: Contact Suzanne Carroll at 781-972-5452 or scarroll@healthtech.com for more information)

12:30 Luncheon Presentation (Opportunity Available) or Lunch on Your Own

Emerging Cancer Immunotherapies 

1:55 Chairperson’s Opening Remarks

John Doukas, Ph.D., Senior Director, Preclinical Safety and Efficacy, Vical, Inc.

2:00 Synergism Between Anti-Tumor Antibodies and PK-Extended IL-2

K. Dane Wittrup, Ph.D., Dubbs Professor, Chemical Engineering and Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

We have found that combination treatment with anti-tumor antibody and an IL-2 Fc fusion exerts a significantly stronger suppression of tumor growth than either agent alone. This effect depends on the presence of both CD8+ T cells and neutrophils, indicating a close cooperation between innate and cellular immunity. Strong potential exists for further synergy between anti-tumor antibodies and the new generation of T cell-directed immunotherapies.

2:30 Identifying New Cancer Immunotherapy Targets for T Cells

Robert Holt, Ph.D., Senior Scientist and Head of Sequencing, British Columbia Cancer Agency, Canada

Effective cancer immunotherapy relies on effective tumor antigens. However, most variations that distinguish tumor cells from normal cells are sporadic, and their immunogenicity is undetermined. High throughput genomic analysis is a useful approach for evaluating the potential immunogenicity of individual tumors and identifying new candidate antigens for follow-on validation. We are using two methods for T cell antigen discovery that will be described, including tumor genome sequencing and computational epitope prediction, plus deep TCR sequencing of tumor-associated T cells.

3:00 Immunomodulatory Antibody-Fusion Proteins for Cancer Immunotherapy

Dafne Müller, Ph.D., Researcher, Institute of Cell Biology and Immunology, University of Stuttgart, Germany

Cytokines of the common cytokine receptor γ-chain family and co-stimulatory members of the B7- and TNF-family have shown great potential to support the generation and development of an antitumor immune response. In order to improve the efficacy of such molecules at the tumor site we designed antibody fusion proteins for therapeutic approaches, focusing either on optimized presentation or a combined mode of action.

3:30 Refreshment Break

4:00 TIM (T Cell Immunoglobulin and Mucin)-3 as a Potential Target for Cancer Immunotherapy

Ana Carrizosa Anderson, Ph.D., Assistant Professor, Neurology, Harvard Medical School

TIM-3 marks both “exhausted” CD8+ T cells and regulatory T cells (Treg) present in solid tumors. TIM-3/PD-1 co-blockade down-modulates Treg suppressor function in Tim-3+ Treg, restores function to exhausted CD8+ T cells, and is highly effective in controlling tumor growth. Thus, TIM-3/PD-1 blockade down-modulates two major mechanisms of immune suppression that are active in tumor-bearing hosts, namely exhausted CD8+ T cells and Treg.

4:30 Allovectin: In vivo Studies and Potential Synergy with other Advanced Melanoma Immunotherapeutics

John Doukas, Ph.D., Senior Director, Preclinical Safety and Efficacy, Vical, Inc.

Allovectin® is a cancer immunotherapeutic currently completing evaluation in a pivotal Phase 3 metastatic melanoma study. Designed for direct intratumoral administration, it is intended to induce antitumor immune responses against both treated and distal lesions by stimulating innate and adaptive immune responses. This presentation will review Allovectin’s proposed mechanisms of action and potential synergy with other immunotherapies, drawing supporting data from preclinical and clinical studies.

5:00 Clinical Update of IL2 Adjunctive Co-Therapy for Suppression of Solid Tumors with Designer T Cells

Richard P. Junghans, M.D., Professor, Department of Medicine, Boston University School of Medicine; Roger Williams Medical Center

IL2, an essential adjunct in therapies with tumor-infiltrating lymphocytes, has not been widely applied in designer T cell interventions, although rationales for supplementation would seem to bridge both settings. This discrepancy may reflect the restricted set of investigators with IL2 experience rather than a biologically motivated choice. Preclinical data establishesthe need for IL2 to eliminate established tumors with dTc, and early clinical data in prostate cancer targeting may be interpreted similarly.

5:30-6:30 Reception in Exhibit Hall with Poster Viewing

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