This proposal deals with practical applications of glycosyl- phoshatidylinositol (GPI) protein tranfer, with the objectives geares towards clinical translation down the road. The overall goal is to develop immunotherapies for cancer which which use eith engineered tumor cells themselves (painted with costimulator-GPI proteins, such as B7-1-GPI and B7-2-GPI) or antigenically engineered professional antigen-presenting cells (APCs)(painted with MHC-GPI. Tumor peptide antigen complexes) as cellular vaccines to elicit systemic anti-tumor responses. Accomplishments to data have contributed towards the use of protein transfer as a tool for producing each of these kinds of cellular vaccines. Significantly, protein transfer, unlike gene transfer, is reality applicable to primary tumor cells and professional APCs that are difficult to transfect and facilitaes the simultanceous expression of multiple proteins at the cell surface. The present proposal consists of five specific amis which are intended to serve as a platform for cancer therapeutics development and later clinical trials with adjuvant cancer vaccines: (1) ex vivo and in vivo studies with B7-1GPI and B7-2-GPI proteins will be completed; (2) The usefulness of other (non-B7) costomulator.GPIs for immunogenic tumore cell engineering, along with other potentially agents, will be evaluated; (3) The feasibilty of generating immunogenic tumor cells in the situ within tumor beds will be determined; (4) Functional studies with HLA-A2.1'GPIs bearing well-defined tumor peptide antigens will be conducted; and (5) Additional developmental work on GPI protein transfer per se will be performed.
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