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