Overview
Billions of dollars are being invested into the cutting-edge research for cancer treatment. Cancer vaccines have the most promising potential to represent the next generation in cancer treatment therapeutics, being more efficient and less toxic than conventional tumor therapies. Identifying new target antigens remains as much of a challenge as improving tumor vaccines already in development. International experts will present the state of the art knowledge on the advantages and disadvantages of using various tools such as DNA Vaccines, Dendritic Cell Approaches, Peptides and Proteins for designing vaccines against tumors. In addition, new strategies to improve the vaccine potency and delivery will be discussed. Discuss with speakers from industry and academia topics such as: ¥ Epitope Identification ¥ Proteomics Based Target Discovery ¥ Developing Viable Tumor Antigens ¥ SAGE as a tool for Cancer Antigen Discovery ¥ Peptide Based Vaccination Strategies ¥ Viral Proteins for Treatment of Cancer ¥ Multivalent Recombinant Vaccines ¥ Heat Shock Protein Vaccines ¥ Nucleic Acid Vaccines ¥ Gene Delivery Systems ¥ Dendritic Cell Based Therapies ¥ Molecular Markers to Predict Vaccine Efficacy Related Links DNAVACCINE.COM Japanese Journal of Cancer Research National Cancer Institute
Agenda
Thursday, May 9, 2002 8:15 Registration, Poster/Exhibit Set Up, Coffee and Pastries9:10 Chairperson's Opening Remarks Nicholas P. Restifo, M.D. 9:15 A Brief History of Cancer Vaccines Nicholas P. Restifo, M.D. A decade ago, it seemed clear that our burgeoning knowledge of the molecular identities of tumor associated antigens would point the way to an effective therapeutic cancer vaccine. Significant progress has been made and objective regressions are observed in some patients with metastatic disease. Notwithstanding this progress, we do not yet have in hand sufficiently reliable cancer vaccines. Promising future directions will be described. Identification of TARGET antigens 9:50 Epitope Identification and Vaccine Design for Cancer Immunotherapy Alessandro Sette, Ph.D., Vice President, Chief Scientific Officer, Epimmune Inc.* Our group has developed processes for engineering multi-epitope vaccines based on the identification and selection of epitope packages with desired characteristics, and also based on vaccine design optimization using epitope placements and spacers to optimize processing efficacy. As these vaccine constructs are designed and optimized, analytical methods are developed to allow testing the immunogenicity and antigenicity of sample epitopes included in the vaccine. In terms of specific disease indications, our epitope identification process has been applied to numerous cancer types and infectious diseases and epitope analog strategies to enhance vaccine design have also been explored. As a result, epitope packages have been defined which allow high, redundant and ethnically balanced patient coverage. We look forward to examining the clinical performance of these novel vaccine constructs in a variety of prophylactic and therapeutic applications in cancer and infectious diseases. *In collaboration with: Elissa Keogh, Glenn Ishioka, John Sidney, Shabnam Tangri, Robert Chesnut and John Fikes10:25 Proteomics-Based Target Discovery: The Key to Development of Effective Therapeutic Cancer Vaccines Stephen L. Hoffman, M.D., Senior Vice President, Biologics, Celera Genomics There is considerable evidence that T cell-mediated immune responses can have a significant impact on the pathology and clinical outcome of a number of cancers. Yet, no cancer vaccines have been shown to reproducibly cure a high percentage of patients with common tumors. The convergence of comparative genomics, molecular immunology, novel vaccine technologies, and the discovery of differentially expressed proteins in specific tumors by high throughput liquid chromatography and mass spectrometry ("proteomics") will accelerate development of effective therapeutic cancer vaccines. 11:00 Refreshment Break and Poster/Exhibit Viewing 11:30 Integrated Protein Expression Profiling with Immunogencity Analyses to Validate Cancer Antigens Robert G. Urban, Ph.D., Vice President, New Technologies and Targets, Zycos Inc. To discover, credential, and develop viable tumor antigens several criteria must be met. 1) The target must be expressed on surface MHC proteins, 2) the human T cells repertoire must contain T cells capable of recognizing the target, and 3) formulations must be developed to elicit anti-tumor immunity in vivo. Systems designed to achieve these three objectives will be discussed in detail. 12:05 Use of SAGE for Cancer Antigen Discovery Bruce L. Roberts, Ph.D., Vice President, Applied Genomics and Immunotherapy, Genzyme Corporation and Genzyme Molecular Oncology We have used SAGE in conjunction with a proprietary high throughput combinatorial peptide screening technology, Solid Phase Epitope Recovery (SPHERE), to identify antigens recognized by cytotoxic T cells and derive altered peptide ligands capable of stimulating potent immune responses. Similarly we have used SAGE in conjunction with an antibody specificity screening technology (Ab-SCAN) to identify secreted and cell surface antigens recognized by cancer patient antibodies. In this manner, SAGE can be used as a versatile functional genomics tool to identify cancer antigens. 12:40 Luncheon, Hosted by The Knowledge Foundation, Inc. Current Vaccine StrategiesSession Chairperson: Bruce L. Roberts, Ph.D., Vice-President, Applied Genomics and Immunotherapy, Genzyme Corporation and Genzyme Molecular Oncology 2:10 Peptide Based Vaccination Strategies Against Tumors Rienk Offringa, Ph.D., Tumor Immunology Group, Dept. of Immunohematology & Blood Transfusion, Leiden University Medical Center, The Netherlands* Experiments in murine tumor models revealed that immunization with peptide-based CTL epitope vaccines can result in the induction of specific CTL immunity capable of eliminating tumor cells. However, whereas such vaccines generally protect mice against a subsequent challenge with tumor cells, the CTL responses induced are rarely capable of eliminating pre-existing tumors. Most CTL epitope vaccines fail to induce therapeutic anti-tumor CTL immunity because antigen-specific priming is not accompanied by provision of the CTL with a true "license to kill". We have recently identified modifications in vaccine design that result in more potent peptide-based vaccines capable of inducing therapeutic anti-tumor immunity. The key factors that make up this "license to kill" are (i) improved antigen delivery to professional antigen presenting cells (APC), (ii) induction of tumor-specific CD4+ T cell help and (iii) delivery of additional signals that trigger activation of APC. *In collaboration with: Sjoerd H. van der Burg, Rene E.M. Toes, Gemma G. Kenter and Cornelis J.M. Melief. 2:45 Therapeutic Vaccines against Melanoma and Colorectal Cancer Philippe Moingeon, Ph.D., Secretary General R&D, Aventis Pasteur France Our overall strategy is to develop multivalent recombinant vaccines capable of eliciting broad immune responses in patients with malignant melanoma or colorectal cancer. I will report results from phases I/II studies conducted in patients with advanced melanoma or colorectal cancer. Our current focus is on the induction of tumor-specific T-cell responses using a prime/boost immunization schedule with a unique vector system derived from the canary pox virus called ALVAC, in which we incorporate genes encoding Tumor Associated Antigens (TAAs) such as Mage 1, Mage 3, KSA or p53. Challenges and opportunities for the development of such vaccines will be discussed. 3:20 Heat Shock Protein Vaccination: Biology and Results Jonathan Lewis, M.D., Ph.D., Chief Medical Officer, Antigenics Inc. This presentation will review the molecular and cell biology of heat shock protein (HSP) in the immune system. It will also discuss the translational biology and clinical trial results. These will include human studies in patients with cancer and viral infections. 3:55 Refreshment Break and Poster/Exhibit Viewing 4:30 Utility of Molecular Markers as Surrogates of Cancer Vaccine Efficacy in Patients Dave S. B. Hoon, M.Sc., Ph.D., Director, Dept. Molecular Oncology, John Wayne Cancer Institute Currently there are limited approaches of assessment of cancer vaccine efficacy in controlling tumor progression in clinically disease-free patients other than disease recurrence or survival. We have developed molecular markers for assessment of the presence of subclinical disease during cancer vaccine treatment. Molecular marker analysis of subclinical disease recurrence can be a valuable surrogate to predict cancer vaccine efficacy early in the course of treatment. 5:05 Development of DNA Vaccine Strategy for Prostate Cancer David B. Weiner, Ph.D., Associate Professor, University of Pennsylvania School of Medicine DNA immunization strategy delivers DNA constructs encoding for a specific immunogen into the host, who becomes the in vivo protein source for the production of antigen. This antigen then is the focus of the resulting immune response. The DNA vaccine approach for the treatment of prostate cancer in rodent and primate animal models will be presented. 5:45 End of Day One Friday, May 10, 20028:30 Coffee and Pastries, Poster/Exhibit Viewing 9:10 Chairperson's Opening Remarks Lorne F. Erdile, Director of Research, AVAX Technologies, Inc. Dendritic Cell-Based Therapies9:15 Dendritic Cell Tumor Fusions as a Novel Cancer Immunotherapy David E. Avigan, M.D., Assistant Professor of Medicine, Harvard University, Beth Israel Deaconess Medical Center This talk will describe the preclinical development of a cancer vaccine in which tumor cells are fused into potent immune stimulating cells known as Dendritic cells. These efforts have led to the development of clinical protocols for the treatment of patients with metastatic breast melanoma and renal cancer. 9:50 Induction of Human Tumor-Loaded Dendritic Cells for Cancer Vaccine Production Carole L. Berger, Ph.D., Research Scientist, Yale University, School of Medicine, Department of Dermatology We report that tumor-loaded dendritic cells (DC) can be developed from peripheral blood monocytes of leukemia patients. The tumor cells are rendered apoptotic at the same time that activated monocytes transition into avidly phagocytic immature DC. During overnight incubation, DC engulf the apoptotic tumor and begin to mature into antigen presenting cells. This rapid procedure is clinically practical, does not involve extensive cellular manipulation or exogenous cytokines and may be extended to other diseases. 10:25 An Efficient Non-Viral Transfection System for Dendritic Cells: Implications for the Immunotherapy of Cancer Dr. Don Healey, Group Leader - Immunology, Cobra Therapeutics, UK We have developed a non-viral transfection system, based on a cationic peptide to condense DNA, to express tumour-associated antigens (TAAs) in dendritic cells. Employing candidate TAAs, we have been able to achieve prophylactic immunotherapy of a murine model of melanoma in vivo, and raise anti-melanoma responses from healthy human volunteers in vitro. A phase I/II clinical trial in melanoma patients will commence in 2002. 11:00 Refreshment Break and Poster/Exhibit Viewing
"naked DNA"-Based Cancer Vaccines11:30 Improving Nucleic Acid Vaccine Potency by Employing Intracellular Targeting and Intercellular Spreading Strategies T.-C. Wu, M.D., Ph.D., Associate Professor, Departments of Pathology, Oncology, Obstetrics and Gynecology, and Molecular Microbiology and Immunology, The Johns Hopkins Medical Institutions Nucleic acid vaccines have emerged as a promising approach for cancer immunotherapy. However, the potency of naked nucleic acid vaccines is limited by their inability to amplify and spread in vivo. We have employed intracellular targeting strategies to enhance MHC class I and II presentation of the encoded antigens and intercellular spreading strategy to increase the number of professional antigen presenting cells expressing encoded antigens. These strategies have resulted in the generation of potent antigen-specific T cell-medicated immune responses and antitumor effects. The impressive pre-clinical data based on these strategies have led to several nucleic acid vaccine trials tentatively scheduled for late 2002. 12:05 GVAX Cancer Vaccines - Clinical Development Kristen M. Hege, M.D., Senior Director, Clinical Research, Cell Genesys, Inc. GM-CSF gene-modified, whole tumor cell vaccines (GVAX®) have been shown to induce potent anti-tumor immunity in pre-clinical models in multiple cancers. Early clinical trials investigating GVAX® autologous tumor cell vaccines in melanoma, prostate, and renal cell cancer confirmed the induction of tumor-specific immune responses, but were limited in commercial feasibility by the prolonged ex vivo cell culture required to generate vaccines using retroviral-mediated gene transfer. Ongoing clinical trials have, therefore, focused on several new vaccine platforms which offer technical and commercial advantages including: 1) allogeneic GM-CSF secreting tumor cells lines (prostate and pancreatic cancer), 2) autologous tumor cells genetically modified with an adenoviral vector to secrete GM-CSF (non-small cell lung cancer), and 3) autologous tumor cells mixed with a GM-CSF-secreting bystander cell line (non-small cell lung cancer, acute myelogenous leukemia, and multiple myeloma). Phase I/II clinical trials of these three vaccine platforms are underway in multiple clinical settings in these five tumor types and results from these studies will be presented. 12:40 Lunch On Your Own
Improving Cancer Vaccines EfficacySession Chairperson: Pierre Lemieux, Ph.D., Head of Gene Delivery/Therapy, Supratek Pharma Inc. 2:15 Poloxamer-Based Gene Delivery Systems Increase Genetic Immunization Against Cancer Pierre Lemieux, Ph.D., Head of Gene Delivery/Therapy, Supratek Pharma Inc. Poloxamers are recognized pharmaceutical excipients listed in the US and British Pharmacopoeia. They have been used extensively in a variety of pharmaceutical formulations especially for the delivery of small molecules and polypeptides. We recently reported that a combination of Poloxamers called SP1017 can be used to formulate plasmid DNA by significantly enhancing intramuscular, intradermal and intratumoral gene expression. Advantages of SP1017 will be presented as well as experimental data supporting it efficacy when applied as a gene delivery system to improve genetic immunization against cancer. 2:50 Current Perspectives on Cancer Vaccines Lorne F. Erdile, Director of Research, AVAX Technologies, Inc. Many approaches are being tried to develop safe and effective cancer vaccines, ranging from whole cell approaches to those focused on defined epitopes, each with its own unique advantages and disadvantages. I will discuss the scientific, regulatory and practical aspects of the various strategies, focusing on haptenized autologous tumor cell vaccines. 3:25 A Novel Therapeutic Approach to Treat Cancer J. Joseph Kim, Ph.D., President and CEO, Viral Genomix, Inc. Viruses are extremely potent in invading and commandeering the host cell functions. They do this by producing specific viral proteins with specific functions. The viral proteins are extremely potent, well-honed tools, which retain their ability to regulate important cell functions even when they are separated from the disease causing parts of the virus. In this regard, these viral proteins represent potent drug candidates developed by millions of years of "in vivo drug screening" in humans. The progress in the use of therapeutic viral proteins as a novel approach for the treatment of cancer will be presented. 4:00 End of Conference
Call for Posters
Call for Posters Industry and academic scientists are encouraged to submit poster titles for this event. One-page abstracts (8 1/2” x 11” with 1-inch margins) must be submitted no later than April 15, 2002 for inclusion in conference documentation. Additional poster submissions will be accepted until May 5, 2002 but may not be included in conference documentation. Note: If you are submitting a poster, you MUST be registered and paid in advance to ensure that a posterboard is reserved for you. Size of Posterboard: 3 x 4 feet (90 x 120 cm)
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Registration fee includes lunch on the first day, refreshments and all documentation made available to us by speakers. Commercial registration: US $1099. Academic/government registration: US $699. Posterboard fee: US $45 (you must be registered) On-site registration:additional $100. The academic/government rate is extended to all participants registering as full time employees of government and universities. To receive the academic/government rate you must not be affiliated with any private organizations either as consultants or owners or part owners of businesses. Payment: All payments must be made in U.S. funds drawn on a U.S. bank. Please make check(s) payable to The Knowledge Foundation, Inc. and attach to the registration form even if you have registered by phone, fax or e-mail. To guarantee your registration, payment must be received prior to the conference. Confirmation of your booking will follow. Discount Accommodations and Travel: A block of rooms has been allocated at a special reduced rate. Please make your reservations by April 10, 2002. Contact The Knowledge Foundation if you require assistance. Venue: Hilton Back Bay 40 Dalton Street Boston, MA 02115 To recieve discount for room reservations contact: Andersen Travel at Phone: (508) 429-6494 or 1-800-229-6494 Fax: (508) 429-7380 Email: suek@andersentvl.com When making reservations, please refer to The Knowledge Foundation's Event. The Knowledge Foundation's official travel agent, Andersen Travel will assist you in making all or a portion of your travel arrangements. Substitutions/Cancellations: A substitute member of your company may replace your attendance at any time at no charge if you find your schedule prevents you from attending. Please notify us immediately so that materials can be prepared. If you do not wish to substitute your registration, we regret that your cancellation will be subject to a $100 processing fee. To receive a prompt refund, we must receive your cancellation in writing 15 days prior to the conference. Unfortunately cancellations cannot be accepted after that date. In the event that The Knowledge Foundation, Inc. cancels an event, The Knowledge Foundation, Inc. cannot resume responsibility for any travel-related costs.
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