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