Human tumor antigens recognized by T lymphocytes.

Abstract

W e have come a long way since the identification of the first human tumor antigen recognized by autologous CTL.This report provides a brief appraisal of these antigens and their potential for cancer immunotherapy.Our comments will be restricted to nonviral antigens.The initial work carried out on mouse tumors revealed two possible mechanisms for generating new antigens that might be suflficiendy tumor-specific to be of relevance to immunotherapy.The first mechanism involved a point mutation, and the second involved the transcriptional activation ofa gene not expressed in normal tissues (1-3).Subsequent work on mouse tumors provided two interesting examples of tumor antigens resulting from point mutations (4, 5).Tumor-specific Shared Antigens.Three families of genes that appear to code for highly specific tumor antigens have been identified so far, namely, the MAGE, BAGE, and GAGE genes (6-9).These genes are frequently expressed in a wide range of tumor types such as melanoma, lung carcinoma, sarcoma, and bladder carcinoma, but very rarely in other tumor types such as brain tumors, renal carcinoma, and leukemia (7,(10)(11)(12).The only normal tissues where expression of these genes has been observed are testis and placenta (7).Starting from CTL clones obtained by stimulating lymphocytes with an autologous melanoma cell line, six antigens encoded by MAGE-1, BAGE, and GAGE have been identified (8,9,[13][14][15].For these six an-