Innovative T Cell-Targeted Therapy for Ovarian Cancer
Annual rept. 30 Sep 2011-29 Sep 2012
M D ANDERSON CANCER CENTER HOUSTON TX
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Major advances have been made in two main areas. Firstly, Receptor tyrosine kinase-like orphan receptor-1 ROR1 was identified as a tumor antigen expressed on ovarian cancer OvCa, but not expressed on normal tissues. Second generation chimeric antigen receptors CARs were designed with CD3z and either CD28 or CD137 endodomains fused to the antigen-binding region of a ROR1-specific monoclonal antibody clone 4A5. CARs were stably expressed in T cells following Sleeping Beauty transposition and propagation on ROR1 artificial antigen presenting cells aAPC. Re-directed cytolysis of ROR1 OvCa cell lines by CAR T cells was demonstrated. Secondly, the anti-tumor activity of y delta T cells was harnessed to kill OvCa. aAPC were used to expand a polyclonal population of y delta T cells for immunotherapy. OvCa xenografts were eliminated by polyclonal y delta T cells.
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