Mutated
p21 ras proteins contain single substituted
amino acid residues and represent
cancer-specific
proteins. The current study examined whether primed T cell immunity to mutant
p21 ras proteins and/or
peptides can be detected in patients with pancreatic or
colon cancer. Studies focused on the
aspartic acid substitution in
amino acid position 12 (denoted D12) as the commonest mutation in gastrointestinal
malignancy. Peripheral blood lymphocytes from patients or normal individuals were tested for the ability to proliferate in response to normal or mutated ras
peptides or
proteins. T-cell responses were defined as a stimulation index of > 2.0. Results showed that 7 of 16 (44%)
pancreatic cancer patients responded to ras-D12
peptide. Responses to ras-D12
protein were studied in only the last four patients that responded to D12
peptides. Three of the 4 patients that responded to ras-D12
peptide showed a substantial response to p21 ras-D12
protein (stimulation indices of 12, 8, and 24). Specificity was validated by examining responses to normal and alternate ras
peptides and
proteins. T-cell responses to ras-D12
peptides were detected in only 2 of 25 (8%)
colon cancer patients. None of 11 normal individuals tested had positive responses to normal or mutant ras p21
proteins and/or
peptides. Thus, CD4+ T-cell immunity to the mutated segment of
ras protein is present in some patients with
gastrointestinal cancer.