Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Challenges and potentials in tumor immunotherapy targeted at the shared tumor antigens

P Zheng MD PhD 1, XF Bai MD PhD 1, J Bender MD 2, Y Liu PhD 1

1 Dept Pathology,, 2 Dept Internal Medicine, Ohio State University Medical Center, Columbus, OH,

AIMS: Technological advances in measuring tumor-reactive CTL provide tumor immunologists with a major surprise: the CTL specific for unmutated tumor antigen have undergone extensive clonal expansion without significantly improvement on the progression of cancers. METHODS: We have developed an adoptive transfer model using the first transgenic mice specific for a natural tumor antigen P1A to investigate the effector function of the tumor reactive CTL in vivo. RESULTS: Multiple lineages of murine tumors, mastocytoma P815, fibrosarcoma Meth A, and plasmocytoma J558 express P1A at high levels and are highly susceptible to cytolysis by the P1A-specific CTL clone from which the transgenic TCR were isolated. Interestingly, a large number of CTL fail to reject any of the three tumors despite rapid T cell clonal expansion and functional maturation of CTL in vivo. Thus the effector function of CTL is restrained in vivo. Importantly, expression of B7 on the tumor cells allowed the CTL to reject all three lineages of tumors, and B7 interact with CTLA4 and CD28 on CTL to promote cognate destruction of tumor cells in vivo. CONCLUSIONS: Our results revealed a major challenge in employment of shared tumor antigen as targets for tumor immunotherapy, and illustrated the vast potential of costimulatory molecules B7, CD28 and CTLA4 as targets for enhancing the effector function of tumor-specific CTL.


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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.