BASIC STUDY OF CLINICAL APPLICATION OF HUMAN MONOCLONAL ANTIBODY TO RAS ONCOGENE PRODUCT

研究胰腺癌和结肠癌患者对ras癌基因产物的免疫应答。胰腺癌和结肠癌患者血清抗ras抗体阳性率分别为80%（4/5）和40%（51/150），显著高于正常人（55，2/40）。抗ras抗体识别p21 ras蛋白的正常或突变片段，并且73%的结肠癌患者具有针对p21 ras蛋白的羧基末端的抗体。胰腺癌和结肠癌患者T淋巴细胞特异性ras肽的检出率分别为40%（6/15）和24%（6/25），显著高于正常人（0%，0/20）。我们尝试从胰腺癌患者的外周血淋巴细胞中诱导针对ras多肽的细胞毒性T淋巴细胞，发现其中一名患者的外周血淋巴细胞可诱导针对p21 ras蛋白正常羧基端的CD 4 + CTL。结果表明，诊断存在的基础上，血清抗体ras致癌蛋白，免疫治疗与特异性细胞毒性T淋巴细胞的ras致癌蛋白是有前途的未来医学治疗胰腺癌和结肠癌患者。

Immune responses to ras oncogenic products were studied in pancreatic and colon cancer patients. Positive rates for serum anti-ras antibody were significantly higher in patients with pancreatic cancer (8O%, 4/5, p<O.05) and colon cancer (40%, 51/150, p<O.Ol) as compared to normal donors (55, 2/40). The anti-ras antibodies recognized normal or mutated segments of p21ras protein, and 73% of colon cancer patients had antibodies to the carboxyl terminus of p2lras protein. T lymphocyte detection rates for specific ras peptides were significantly higher in patients with pancreatic cancer (40%, 6/15, p<O.Ol) and colon cancer (24%, 6/25, p<O.Ol) as compared to normal donors (0%, 0/20). We attempted to elicit cytotoxic T lymphocyte for ras peptides, and found the CD4+ CTL specific for the normal carboxyl terminus of the p2lras 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 treatments for pancreatic and colon cancer patients.