Day Two:

Tuesday, September 21

T-Cell Based Immunotherapy

8:25 Chairperson's Remarks
Michael Salgaller, Ph.D., Senior Associate, Toucan Capital Corp.

8:30 Significance and Optimization of Recognition Efficiency for T Cell Responses to Cancer
Peter P. Lee, M.D., Assistant Professor of Medicine, Stanford University
It is increasingly recognized that an antigen-specific T cell response against a single peptide may be very diverse in terms of TCR usage. Importantly, this translates into significant differences in recognition efficiency of these T cells for target cells expressing the cognate peptide. We have found that within a population of peptide-specific T cells which are indistinguishable by tetramer staining or in ELISPOT analysis, there could be a >1000 fold difference in cognate peptide requirement for target lysis by these T cells. Only T cells of high recognition efficiency efficiently lyse tumor cells. Thus, it is important to understand not only the numbers of antigen-specific T cells elicited by various immunotherapeutic strategies, but also the recognition efficiency of these cells. Ultimately, strategies which preferentially elicit high recognition efficiency T cells should be more successful.

9:00 Xcellerated™ T Cells: The Process, the Biology, Current and Future Clinical Applications
Ron Berenson, M.D., President, CEO, Xcyte Therapies, Inc.
In the setting of cancer, weak or defective immune responses are often observed concomitant with disease progression. We have focused on developing procedures for correcting immunological defects and boosting the activity of the T cell arm of the immune system as a therapeutic strategy for treating cancer. Using a closed-system process for activating and expanding T cells outside the body, patients' T cells are cultured with Xcyte™Dynabeads®, which are microscopic superparamagnetic beads with anti-CD3 and anti-CD28 antibodies attached to their surface. T cells activated by this method (Xcellerated™ T Cells) have been grown to large numbers ex-vivo and infused back into patients with hematological malignancies, such as multiple myeloma and chronic lymphocytic leukemia. During the T cell expansion process, functional and phenotypic defects in patient's T cells are diminished, and marked biological effects have been observed in patients following treatment with autologous Xcellerated™ T Cells.

9:30 New Antigens for Therapeutic Vaccines Against Breast Cancer
Laszlo Radvanyi, Ph.D., Senior Research Scientist, Immunology Platform, Aventis Pasteur
New antigens with more comprehensive coverage and more favorable immunologic profiles are needed to develop active vaccines against breast cancer. Aventis Pasteur has launched a breast cancer vaccine development program involving new antigen discovery, pre-clinical evaluation of potential new targets, and clinical development using poxvirus vectors. So far, the program has yielded the discovery of 5 new vaccine targets with one antigen, called BFA4, found to be one of the most highly expressed and tumour specific antigens in breast cancer found to date. 

10:00 Immunotherapy via CTLA-4 Blockade -Update on MDX-010
Israel Lowy, M.D., Ph.D., Director, Clinical Sciences and Infectious Diseases, Medarex, Inc.
CTLA-4 is a key negative regulator of cellular immune responses, and its blockade results in enhanced anti-tumor responses in a variety of animal models. Clinical experience with MDX-010, a fully human MAb that blocks CTLA-4, has shown the ability to break immunological tolerance to tumors and result in significant and durable clinical responses, and has been well tolerated. MDX-010 is currently in advanced trials in metastatic melanoma, both as monotherapy and in combination with vaccines. It is also under study in malignancies such as prostate, renal cell, breast, lymphoma and ovarian cancer, as well for chronic infections such as HIV. The current state of clinical development with MDX-010 will be discussed.

10:30 Coffee Break, Poster and Exhibit Viewing

Antigen Presenting Cells

11:15 Dendritic Cell/Tumor Fusions as Cancer Immunotherapy
David Avigan, M.D., Director, Hematologic Malignancy/Bone Marrow Transplant Program, Beth Israel Deaconess Medical Center 
I will describe the development of dendritic cell/tumor fusions from pre-clinical models to the clinic. Data from several clinical trials will be reviewed. Biology of fusion cells as antigen presenting cells will be described.

11:45 Clinical Studies Utilizing Polymeric Microparticles for In Vivo Targeting of Antigen Presenting Cells
Dr. Mary Lynne Hedley, Senior Vice President, R&D, ZYCOS Inc
Preclinical studies have demonstrated the safety and usefulness of polymeric microparticle formulations for targeting antigen to APCs in vivo and stimulating effective antigen-specific immune responses. The formulations are stable for at least 3 years, they are easily manufactured, and production has been scaled to support Phase 3 clinical studies. Three different antigen encoding formulations have demonstrated safety and tolerability in clinical studies, and in a Phase 2 placebo controlled, randomized, and blinded study, one of these formulations was tested and found to be efficacious in the treatment of precancerous lesions of the uterine cervix. A second formulation, designed for the treatment of multiple cancer types, was found in a clinical study to be immunogenic and certain patients treated with the formulation in this open label study demonstrated indications of clinical effect. Ongoing results from this trial and a description of the currently planned Phase 3 trial for women with precancerous cervical lesions will be discussed.

12:15 Lunch on Your Own (Sponsorship available)

1:40 Chairperson's Remarks
Tony Mills, Vice President, Business Development, BioVex Ltd.

1:45 Targeted Immunotherapy of Cancer 
Reiner Laus, M.D., Vice President of Research and Development, Dendreon Corporation
Dendreon is developing targeted, immune-based approaches towards the therapy of malignant tumors. Our clinically most advanced product, Provenge, a therapeutic prostate cancer vaccine, has completed a phase III double-blind, placebo controlled trial for treatment of men with hormone-refractory prostate cancer. Additional vaccines for treatment of breast cancer, colon cancer and ovarian cancer are currently in phase I and phase II clinical studies. The vaccines proved to be safe and well tolerated. We will discuss recent data relating to safety and efficacy of our therapeutics. Specifically, we will address the impact of our vaccines on time to objective disease progression, development of pain and on survival. Furthermore, we will share recent insights into the immune mechanisms that mediate the therapeutic effect.

2:15 Telomerase - Based Cancer Vaccine
Anish S. Majumdar, Ph.D., Director of Immunology, Geron Corporation
Telomerase reverse transcriptase (hTERT) is critical for the maintenance of telomere length and chromosomal integrity during cellular replication. HTERT is usually silent in normal somatic tissues, but reactivation and over-expression of hTERT occur in most human tumors to maintain immortality of the tumor cells. Several studies have shown that human tumor cells express telomerase peptides bound to MHC Class I molecules, and these cells could be killed by antigen specific cytotoxic T lymphocytes (CTL). Therefore, hTERT may represent a universal cancer antigen that can be targeted by ex vivo or in vivo vaccination therapy.

2:45 Refreshment Break, Poster and Exhibit Viewing

From Bench to Market

3:15 Entrepreneurship in Cancer Immunotherapeutics: Some Keys to Success in a Pills-and-Bottles World
Michael Salgaller, Ph.D., Senior Associate, Toucan Capital Corp.
Off-the-shelf drugs represent an entrenched doctrine more comfortable and palatable to potential financial and industrial partners. In contrast, immunotherapy presents unique challenges in the path from research lab to pivotal trial. This presentation will provide a primer for those looking to expand a start-up company, begin such a venture, or explore the commercial potential of academic studies. It will also offer to academics, financiers, and companies, some keys to best develop a mutually beneficial relationship.

3:45 Program Management for Cancer Vaccine Development
Antony Newton, Senior Director, Program Management, Genzyme Corporation
Cancer Vaccine programs have complex development pathways. The management of a typical program through defined stage transitions will be described. The effective functioning and make up of a multi-functional core team will be discussed along with the core team's relationship with broader management and outside functions. Some of the typical challenges faced by a cancer vaccine core team will be outlined. A number of tools may be employed to assist in the effective management of a program. Effective core team functioning requires use of team feedback techniques in order to continuously improve the process.

4:15 Cost Effective Manufacture of Autologous Products - Fact or Fiction?
Mario Dipaola, Ph.D., Senior Director of Manufacturing Operations, Antigenics, Inc.
Autologous vaccines represent a new manufacturing paradigm relative to off-the-shelf products. Manufacturing lot sizes are small and scale-up from pilot to commercial scale involves increasing the number of manufacturing lots rather than increasing lot size. Cost effective product manufacturing requires proper process design as well as appropriate analysis methodologies given the large number of manufacturing lots to be released. The holy grail of commercial manufacturing operations is to produce a consistent product. However, by definition every lot of an autologous product is different. The challenge is to define consistency in a manner that can accommodate the inherent uniqueness of the autologous product. This presentation draws upon experiences gained in the development of Oncophage®, a heat shock protein-based autologous therapeutic cancer vaccine.

4:45 Panel Discussion

5:15 End of Conference