Coggin J H, Barsoum A L, Rohrer J W
Department of Microbiology and Immunology, University of South Alabama, College of Medicine, Mobile 36688-0002, USA.
Anticancer Res. 1999 Nov-Dec;19(6C):5535-42.
Based upon positive immunologic comparisons, protein and cDNA sequencing, and in vitro and in vivo immunogenicity studies we propose that carcinomas, sarcomas and lymphomas/leukemias of rodents and humans share 37 kDa Onco-Fetal Antigen [OFA] as a T and B-lymphocyte stimulating, universal tumor specific transplantation antigen [UTSTA]. In the past four years, biochemical studies from several laboratories studying laminin receptor protein and immunological studies of OFA from our laboratories independently converged. OFA protein and immature or precursor Laminin Receptor Protein [iLRP] are > 99% identical proteins based on amino acid and cDNA sequencing and immunobiology studies summarized here. Acquired expression of 37 kDa OFA/iLRP enables malignant tumor cells to penetrate laminin tissue and vessel barriers. 37 kDa OFA/iLRP activates precursor thymic anti-OFA/iLRP specific cytotoxic T cell which kill emerging pretumor cells. Our reported findings also demonstrate that OFA/iLRP can function to induce specific immunoregulatory CD8 T-suppressor cells secreting IL-10 which impair effector T-cell killing of emerging tumor cells non-specifically and thereby facilitate tumor progression. Potential applications of OFA/iLRP detection in early cancer formation, for monitoring patient T cell subclass responses to OFA/iLRP as a predictor of tumor progression, and the use of OFA/iLRP peptides for specific anti-tumor immunotherapy are presented.
基于阳性免疫比较、蛋白质和cDNA测序以及体内外免疫原性研究,我们提出啮齿动物和人类的癌、肉瘤以及淋巴瘤/白血病共享37 kDa肿瘤胚胎抗原[OFA],作为一种刺激T和B淋巴细胞的通用肿瘤特异性移植抗原[UTSTA]。在过去四年中,几个研究层粘连蛋白受体蛋白的实验室的生化研究以及我们实验室对OFA的免疫学研究独立地得出了相同结论。根据氨基酸、cDNA测序以及本文总结的免疫生物学研究,OFA蛋白与未成熟或前体层粘连蛋白受体蛋白[iLRP]的同源性超过99%。37 kDa OFA/iLRP的获得性表达使恶性肿瘤细胞能够穿透层粘连蛋白组织和血管屏障。37 kDa OFA/iLRP激活胸腺前体抗OFA/iLRP特异性细胞毒性T细胞,这些细胞会杀死新出现的癌前细胞。我们报道的研究结果还表明,OFA/iLRP可诱导分泌IL-10的特异性免疫调节性CD8 T抑制细胞,这些细胞会非特异性地损害效应T细胞对新出现肿瘤细胞的杀伤作用,从而促进肿瘤进展。本文还介绍了OFA/iLRP检测在早期癌症形成中的潜在应用、监测患者T细胞亚类对OFA/iLRP的反应以预测肿瘤进展,以及使用OFA/iLRP肽进行特异性抗肿瘤免疫治疗。