Human tumors elicit multiple specific immune responses in the autologous host. The study identified at least four antigens with restricted expression in each tumor type. These antigens, including known T-cell targets like MAGE-1 and tyrosinase, were found to be overexpressed or specifically expressed in tumors of the same type. Sequence analysis suggests these molecules may be relevant to tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be defined at the molecular level by autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host, providing diagnostic and therapeutic approaches to human cancer. A prerequisite for the successful application of recombinant tumor vaccines and other immunotherapeutic interventions in cancer patients is the recognition by the immune system of tumor-specific and tumor-associated antigens. Despite extensive efforts to identify such antigens, only few have been defined at the molecular level. B-cell responses (antibodies) have been demonstrated in cancer patients when searching for antibodies against predefined molecules expressed by human tumors. New and known molecules were identified as tumor antigens by analyzing the T-cell repertoire against tumors using two strategies: a genetic approach and a biochemical strategy. Using these approaches, several additional human tumor antigens have been defined at the molecular level, most notably in malignant melanoma. For many human tumors other than melanoma, tumor antigens have yet to be defined at the molecular level. The study used a strategy of "serological identification of antigens by recombinant expression cloning" (SEREX) to discover an unexpected frequency of tumor antigens that elicit specific immune responses in the autologous host. The results showed that the melanoma antigen HOM-MEL-40 was strongly expressed in melanomas but absent in other tissues except for normal testis. The carbonic anhydrase-like protein (HOM-RCC-3.1.3) was strongly overexpressed in approximately 20% of renal cell carcinomas compared to normal renal tissue. The TEGT gene was overexpressed in 8 of 12 astrocytomas compared to normal human brain tissues. The HOM-HD-21 antigen was increased about 10-fold in diseased tissue compared to normal tonsils. The occurrence of antibodies against tumor antigens was found to be more common in patients with the same type of tumor. The clinical significance of B-cell responses to tumor antigens is unknown. However, the study suggests that an integrated immune response against tumor antigens may exist that involves both CD8⁺ and CD4⁺ T cells as well as B cells. The molecular definition of tumor antigens by SEREX of tumor cDNA is fast and has a high yield, making it a useful tool for defining tumor antigens and analyzing their role in T-cell immunityHuman tumors elicit multiple specific immune responses in the autologous host. The study identified at least four antigens with restricted expression in each tumor type. These antigens, including known T-cell targets like MAGE-1 and tyrosinase, were found to be overexpressed or specifically expressed in tumors of the same type. Sequence analysis suggests these molecules may be relevant to tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be defined at the molecular level by autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host, providing diagnostic and therapeutic approaches to human cancer. A prerequisite for the successful application of recombinant tumor vaccines and other immunotherapeutic interventions in cancer patients is the recognition by the immune system of tumor-specific and tumor-associated antigens. Despite extensive efforts to identify such antigens, only few have been defined at the molecular level. B-cell responses (antibodies) have been demonstrated in cancer patients when searching for antibodies against predefined molecules expressed by human tumors. New and known molecules were identified as tumor antigens by analyzing the T-cell repertoire against tumors using two strategies: a genetic approach and a biochemical strategy. Using these approaches, several additional human tumor antigens have been defined at the molecular level, most notably in malignant melanoma. For many human tumors other than melanoma, tumor antigens have yet to be defined at the molecular level. The study used a strategy of "serological identification of antigens by recombinant expression cloning" (SEREX) to discover an unexpected frequency of tumor antigens that elicit specific immune responses in the autologous host. The results showed that the melanoma antigen HOM-MEL-40 was strongly expressed in melanomas but absent in other tissues except for normal testis. The carbonic anhydrase-like protein (HOM-RCC-3.1.3) was strongly overexpressed in approximately 20% of renal cell carcinomas compared to normal renal tissue. The TEGT gene was overexpressed in 8 of 12 astrocytomas compared to normal human brain tissues. The HOM-HD-21 antigen was increased about 10-fold in diseased tissue compared to normal tonsils. The occurrence of antibodies against tumor antigens was found to be more common in patients with the same type of tumor. The clinical significance of B-cell responses to tumor antigens is unknown. However, the study suggests that an integrated immune response against tumor antigens may exist that involves both CD8⁺ and CD4⁺ T cells as well as B cells. The molecular definition of tumor antigens by SEREX of tumor cDNA is fast and has a high yield, making it a useful tool for defining tumor antigens and analyzing their role in T-cell immunity