PROSTATE CANCER VACCINE BY SUPPRESSING Ii PROTEIN

DESCRIPTION: Suppressing the Ii protein by anti-sense oligonucleotides in MHC class Il-positive cancer cells creates a potent cancer cell vaccine. Presumably, additional determinants which are normally excluded in the ER by the Ii protein from the MHC class II antigenic peptide binding site, stimulate a potent and long lasting T helper cell response which guarantees (through dendritic cell 'licensing') a tumor-clearing T killer cell response. We have proved this point in two murine cancer models and identified the most active lead drug. We now focus on prostate cancer because there are no life savings therapies once tumor recurs in patients with an otherwise healthy immune system. Adequate tumor is available in 50 percent of patients at primary resection, and in all early during recurrence. Tumor is also then accessible to injection in situ with liposomes and immunoliposomes containing the lead drug. First, we have begun to validate Ii protein suppression methods in human prostate cancer cell lines (in anticipation of preparing cancer cell vaccines under Phase II). Second, we will optimize cell vaccine dose and dosing schedule in the murine RM-9 prostate cancer model, as we have done in two previous murine tumor models. Third, we will use the optimized cell vaccine regimen plus GM-CSF (and subsequently lL-2) to treat mice with established subcutaneous and orthotopic RM-9 tumors. Subsequent studies in Phase II will focus on the use of fresh human tissues, the inclusion of radiation in the treatment of advanced RM-9 tumors and a pre-IND conference with the FDA. PROPOSED COMMERCIAL APPLICATION: Tumor cell vaccine for prostate, breast, ovarian and colon cancer. In situ immunotherapy of metastates enhancement or dendritic cell immunotherapies for cancer.