""""""""DISCONTINUED The ras proto-oncogene is activated by point mutation in approxi- mately 30% of human cancers, pancreas, and lung. K-ras mutations are found in approximately 40% of colon carcinomas, 25% of lung adeno- carcinomas, and 90% of pancreatic adenocarcinomas. Murine systems demonstrate that combining soluble mutant ras proteins with novel adjuvants such as QS- 21 can result in the generation of proliferative and lytic T cell protective immunity directed specifically at tumor cells expressing specific mutant ras proteins. Treatment of mice bearing palpable tumor nodules led to cures of 50% of the animals. The objectives of this study are: 1) determine the toxicities of combining QS-21 with purified ras proteins, 2) characterize cellular and humoral immune responses, 3) determine if the immunologic responses can be correlated with specific MHC alleles and, 4) correlate immune responses with clinical responses. The plan is to immunize pts. with the following characteristics: 1. Dukes C colon cancer; 2. Stage II or III adenocarcinoma of the lung; 3. Pancreatic cancer patients. If a ras mutation is present that corresponds to one of the four forms of K-ras we have produced (position 12 Asp, Val, Cys; position 13 Asp), the pt. will be vaccinated as follows: Cohort 1, 2, and 3 will receive 100 &g of QS-21 mixed with escalating of doses of ras protein (50, 250, or 1000 &g). Cohorts 4-6 will receive 200 g of QS-21 with the same dose escalation of ras protein. The vaccine ill be administered subcutaneously every 2 wks. for 4 vaccinations. We plan to accrue 36 pts. One patient with Stage II carcinoma has been vaccinated and remains free of disease. Accrual has been slow. Consideration is being given to change eligibility criteria to include patients with metastatic disease.""""""""
