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Cancer Immunotherapy • • • • Manipulation of co-stimulatory signals Enhancement of APC activity Cytokine therapy Monoclonal antibody therapy Co-stimulatory signals • Possibility of transfecting irradiated (inactivated) tumor cells with B7 co-stim genes – Perhaps a similar vaccine may prevent metastasis after surgical removal of tumors Also, melanoma antigens shared by a number of different tumors Enhancement of APC activity • Transfect tumor cells with gene encoding GM-CSF reinfuse to patient to stimulate DC’s to enhance Ag presentation to TH’s and Tc’s • Or culture patient DC’s w/ GM-CSF, TNF-a, and IL-4 expand DC population • Or use adjuvants of (Mb, Cp) to stimulate MØ to better activate TH cells??? Cytokine therapies • From cloned genes for various cytokines (IFN’s, TNF’s, etc.)….still a work in progress • IFN’s – daily injections of IFN-a – partial/complete tumor regression All 3 types of IFN >MHC I on tumor cells; >CTL response All 3 appear to inhibit cell division in tumor cells IFN-y stim activity of Tc’s, MØ, and NK cells Cytokine therapies (cont’d) • TNF’s – both TNF-a/B show direct effects on tumor cells, while sparing normal cells – TNF-a shows anti-angiogenic affects to tumors • ↓blood flow and oxygen Monoclonal antibodies