A Survey of Diagnosis of Existence and Immunotherapy with Immune Response to ras Oncogenic Proteins in Pancreatic and Colon Cancer Patients

Masazumi Takahashi, Hiroyuki Yamaoka, Yasushi Ichikawa, Shinji Togo, Hiroshi Shimada, Martin A Cheever*

Second Department of Surgery, School of Medicine, Yokohama City University
*Division of Oncology Department of Medicine, School of Medicine, University of Washington

Immune responses to ras oncogenic proteins were studied in pancreatic and colon cancer patients. Positive rates for serum anti-ras antibody were significantly higher in patients with pancreatic cancer (80%, 4/5, p<0.05) and colon cancer (40%, 51/150, p<0.01) as compared to normal donors (5%, 2/40). The anti-ras antibodies recognized normal or mutated segments of p21 ras protein, and 73% of colon cancer patients had antibodies to the carboxyl terminus of p21 ras protein. T lymphocyte detection rates for specific ras peptides were significantly higher in patients with pancreatic cancer (40%, 6/15, p<0.01) and colon cancer (24%, 6/25, p<0.01) as compared to normal donors (0%, 0/20). We attempted to elicit cytotoxic T lymphocytes (CTL) specific for ras peptides, and found that CD4⁺ CTL specific for the normal carboxyl terminus of the p21 ras protein could be elicited from peripheral blood lymphocytes from one of the three patients with pancreatic cancer. The results suggest that diagnosis of the existence, based on serum antibodies to ras oncogenic proteins, and immunotherapy with CTL specific for ras oncogenic proteins are promising future medical treaments for pancreatic and colon cancer patients.

Key words
ras oncogene, tumor specific antigen, pancreas cancer

Reprint requests
Masazumi Takahashi Second Department of Surgery, School of Medicine, Yokohama City University
3-9 Fukuura, Kanazawa-ku, Yokohama, 236 JAPAN

Accepted
December 11, 1996

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