The 13th Annual Meeting 2007 Japan Society of Gene Therapy : Date June 28–30, 2007 Venue International Conference Hall (Aichi Cancer Center) 1–1, Kanokoden, Chikusa–ku, Nagoya, Japan JSGT Website:http://jsgt.jp

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 682 KB
• Volume: 10
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1175

✦ Synopsis

Our most powerful line of defense against invading pathogens, the immune system, is largely ineffective against cancers. Despite unequivocal evidence that the immune system is capable of eliminating bulky metastatic disease, antitumor immune responses are largely ineffective because of: (1) inadequate precursor frequency of tumor-specific T cells, (2) the subdominance of ''self'' tumor antigens and (3) antipoptotic genetic programs in tumor targets conferring resistance to cell-mediated cytotoxicity. Inadequate precursor frequency can be addressed through engineering of T cells and/or hematopoietic stem cells with high affinity T cell receptors (TCR) that recognize defined common tumor antigen in the context of the major histocompatibility antigen complex. Recent preclinical advances lentiviral engineering of human melanoma-specific TCR will be presented. Most human tumor antigens are ''self'' and generally elicit weak, low affinity T cell expansion. Improvements in vaccine design, particularly dendritic cell and virally based vaccines, combined with toll-like receptor agonists and immunomodularity therapies (CTLA-4 blockade) have the potential to elicit enhanced T cell responses and with broadened specificities. Finally, even in the setting of an otherwise effective antitumor immune response, tumors have frequently acquired genetic resistance to apoptosis. Novel small molecules that target these antiapoptotic gene programs can be effectively interfaced with immunotherapy in preclinical animal models. Preclinical and clinical advances for melanoma will be presente.