The article by Thierry Boon and Pierre van der Bruggen provides an overview of human tumor antigens recognized by T lymphocytes, focusing on nonviral antigens. The authors discuss the mechanisms by which new antigens are generated, such as point mutations and transcriptional activation of genes not expressed in normal tissues. They highlight three families of genes—MAGE, BAGE, and GAGE—that code for highly specific tumor antigens, which are frequently expressed in various cancers but rarely in other types. These antigens have been identified in melanoma, lung carcinoma, sarcoma, and bladder carcinoma, with expression observed only in testis and placenta. The authors also discuss the potential for immunotherapy using these antigens, noting that the expression of relevant genes in germline cells should minimize harmful side effects. The article further explores tumor-specific shared antigens, including mucin antigens recognized by CTL against breast, ovarian, and pancreatic carcinomas, and differentiation antigens like tyrosinase, Melan-A/Mart-1, gp100, and gp75. The authors discuss the potential for immunotherapy using these antigens, considering both the benefits and concerns regarding side effects. Additionally, the article examines antigens generated by point mutations, which are specific to individual tumors and may be difficult to develop into therapeutic vaccines. The authors also discuss ubiquitous antigens and the use of "reverse immunology" to identify antigens encoded by MAGE genes and mutated oncogenes. Finally, the authors reflect on the potential of antigens identified through direct immunology versus those identified through reverse immunology, emphasizing the need for clinical trials to determine their effectiveness in immunotherapy. They express hope that future research will lead to effective antitumor responses and the identification of additional antigens.The article by Thierry Boon and Pierre van der Bruggen provides an overview of human tumor antigens recognized by T lymphocytes, focusing on nonviral antigens. The authors discuss the mechanisms by which new antigens are generated, such as point mutations and transcriptional activation of genes not expressed in normal tissues. They highlight three families of genes—MAGE, BAGE, and GAGE—that code for highly specific tumor antigens, which are frequently expressed in various cancers but rarely in other types. These antigens have been identified in melanoma, lung carcinoma, sarcoma, and bladder carcinoma, with expression observed only in testis and placenta. The authors also discuss the potential for immunotherapy using these antigens, noting that the expression of relevant genes in germline cells should minimize harmful side effects. The article further explores tumor-specific shared antigens, including mucin antigens recognized by CTL against breast, ovarian, and pancreatic carcinomas, and differentiation antigens like tyrosinase, Melan-A/Mart-1, gp100, and gp75. The authors discuss the potential for immunotherapy using these antigens, considering both the benefits and concerns regarding side effects. Additionally, the article examines antigens generated by point mutations, which are specific to individual tumors and may be difficult to develop into therapeutic vaccines. The authors also discuss ubiquitous antigens and the use of "reverse immunology" to identify antigens encoded by MAGE genes and mutated oncogenes. Finally, the authors reflect on the potential of antigens identified through direct immunology versus those identified through reverse immunology, emphasizing the need for clinical trials to determine their effectiveness in immunotherapy. They express hope that future research will lead to effective antitumor responses and the identification of additional antigens.