题目：Immunological insights on immortality, self-renewal and cancer
报告人：Prof.Maurizio Zanetti
University of California, San Diego
Department of Medicine and Cancer Center
时间：2010年5月26日 下午2:30
地点：苏州大学独墅湖校区炳麟图书馆820会议室
Maurizio Zanetti, MD
Professor IR, Medicine
Tumor Growth, Invasion & Metastasis Program
Contact by Email
Diseases/Research Topics
Leukemia, Leukemias and Lymphoma, Lymphoma, Melanoma
Dr. Zanetti and his team have focused on two key immunological issues in cancer. The first is to develop a principle to render immunogenic tumor antigens that otherwise lack completely or in part immunogenicity. It is known that the immune response to Th cell determinants of tumor antigens is often poor and limits severely the potential efficacy of current therapeutic measures through vaccination.
In a series of experiments Dr. Zanetti and colleagues demonstrated that an immunologically-silent tumor determinant can be rendered immunogenic if linked with a dominant determinant of a parasite antigen, suggesting the existence of functional Th-Th cooperation in vivo. This phenomenon appears to be mediated at least in part by signaling through CD40. These findings are new and relevant to understand the immunogenicity of Th cell determinants, and offer new practical solutions for vaccine therapy against cancer and other diseases.
The second line of study involves the development of a universal cancer vaccine. Dr. Zanetti has focused his attention on telomerase, a ribonucleoprotein enzyme which has been linked to malignant transformation in human cells. Telomerase activity is increased in the vast majority of human tumors making its gene product the first molecule common to all human tumors. The generation of endogenously-processed telomerase peptides bound to Class I major histocompatibility complex (MHC) molecules could therefore target cytotoxic T lymphocytes (CTL) to tumors of different origins. This could advance vaccine therapy against cancer provided that precursor CTL recognizing telomerase peptides in normal adults and cancer patients can be expanded through immunization. Dr. Zanetti and colleagues demonstrated that the majority of normal individuals and patients with prostate cancer immunized in vitro against two HLA-A2.1 restricted peptides from telomerase reverse transcriptase (hTRT), develop hTRT specific CTL. This suggests the existence of precursor CTL for hTRT in the repertoire of normal individuals and in cancer patients. Most importantly, cancer patient's CTL specifically lysed a variety of HLA-A2+ cancer cell lines, demonstrating immunological recognition of endogenously-processed hTRT peptides. Moreover, in vivo immunization of HLA-A2.1 transgenic mice generated a specific CTL response against both hTRT peptides. Based on the induction of CTL responses in vitro and in vivo, and the susceptibility to lysis of tumor cells of various origins by hTRT CTL, they suggest that hTRT could serve as a universal cancer vaccine for humans.