Kawakami Y, Eliyahu S, Delgado C H, Robbins P F, Sakaguchi K, Appella E, Yannelli J R, Adema G J, 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 Jul 5;91(14):6458-62. doi: 10.1073/pnas.91.14.6458.
The cultured T-cell line TIL1200, established from the tumor-infiltrating lymphocytes (TILs) of a patient with advanced metastatic melanoma, recognized an antigen on most HLA-A2+ melanomas and on all HLA-A2+ cultured neonatal melanocytes in an HLA-A2 restricted manner but not on other types of tissues or cell lines tested. A cDNA encoding an antigen recognized by TIL1200 was isolated by screening an HLA-A2+ breast cancer cell line transfected with an expression cDNA library prepared from an HLA-A2+ melanoma cell line. The nucleotide and amino acid sequences of this cDNA were almost identical to the genes encoding glycoprotein gp100 or Pmel17 previously registered in the GenBank. Expression of this gene was restricted to melanoma and melanocyte cell lines and retina but was not expressed on other fresh or cultured normal tissues or other types of tumor tested. The cell line transfected with this cDNA also expressed antigen recognized by the melanoma-specific antibody HMB45 that bound to gp100. A synthetic 10-amino acid peptide derived from gp100 was recognized by TIL1200 in the context of HLA-A2.1. Since the administration of TIL1200 plus interleukin 2 resulted in regression of metastatic cancer in the autologous patient, gp100 is a possible tumor rejection antigen and may be useful for the development of immunotherapies for patients with melanoma.
从一名晚期转移性黑色素瘤患者的肿瘤浸润淋巴细胞（TIL）建立的培养T细胞系TIL1200，以HLA - A2限制的方式识别大多数HLA - A2 +黑色素瘤以及所有HLA - A2 +培养的新生儿黑色素细胞上的一种抗原，但不识别所测试的其他类型组织或细胞系上的该抗原。通过筛选用从HLA - A2 +黑色素瘤细胞系制备的表达cDNA文库转染的HLA - A2 +乳腺癌细胞系，分离出编码TIL1200识别的抗原的cDNA。该cDNA的核苷酸和氨基酸序列与先前在GenBank中登记的编码糖蛋白gp100或Pmel17的基因几乎相同。该基因的表达仅限于黑色素瘤、黑色素细胞系和视网膜，但在其他新鲜或培养的正常组织或所测试的其他类型肿瘤上不表达。用该cDNA转染的细胞系也表达与gp100结合的黑色素瘤特异性抗体HMB45识别的抗原。在HLA - A2.1背景下，TIL1200识别源自gp100的合成10氨基酸肽。由于给予TIL1200加白细胞介素2导致自体患者的转移性癌症消退，gp100是一种可能的肿瘤排斥抗原，可能有助于开发黑色素瘤患者的免疫疗法。
