Kawakami Y, Eliyahu S, Delgado C H, Robbins P F, Rivoltini L, Topalian S L, Miki T, Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9. doi: 10.1073/pnas.91.9.3515.
By cDNA expression cloning we have isolated a gene encoding a shared human melanoma antigen recognized by HLA-A2 restricted autologous and allogenic tumor-infiltrating lymphocytes (TILs) from patients with metastatic melanoma. By using both transient and stable expression systems, transfection of this gene into non-antigen-expressing HLA-A2+ cell lines resulted in recognition by the antigen-specific TILs. The sequence of this cDNA revealed a previously undescribed putative transmembrane protein whose expression was restricted to melanoma and melanocyte cell lines and human retina but no other fresh or cultured normal tissues tested or other tumor histologies. Thus, we have identified a gene encoding a melanocyte lineage-specific protein (MART-1; melanoma antigen recognized by T cells 1) that is a widely shared melanoma antigen recognized by the T lymphocytes of patients with established malignancy. Identification of this gene opens possibilities for the development of immunotherapies for patients with melanoma.
通过cDNA表达克隆，我们从转移性黑色素瘤患者中分离出一个基因，该基因编码一种共享的人类黑色素瘤抗原，可被HLA - A2限制的自体和同种异体肿瘤浸润淋巴细胞（TILs）识别。通过使用瞬时和稳定表达系统，将该基因转染到不表达抗原的HLA - A2 +细胞系中，可被抗原特异性TILs识别。该cDNA序列揭示了一种以前未描述的假定跨膜蛋白，其表达仅限于黑色素瘤、黑素细胞系和人类视网膜，而在测试的其他新鲜或培养的正常组织或其他肿瘤组织学中均未表达。因此，我们鉴定出一个编码黑素细胞谱系特异性蛋白（MART - 1；T细胞识别的黑色素瘤抗原1）的基因，它是已确诊恶性肿瘤患者的T淋巴细胞广泛识别的共享黑色素瘤抗原。该基因的鉴定为黑色素瘤患者免疫疗法的开发开辟了可能性。
