Adoptive cell therapy (ACT) is a personalized cancer immunotherapy that involves transferring immune cells with direct anticancer activity into cancer patients. This approach has shown success in treating melanoma by using tumor-reactive lymphocytes that target somatic mutations unique to each cancer. ACT has been expanded to treat common epithelial cancers through genetic engineering of lymphocytes to express T cell receptors (TCRs) or chimeric antigen receptors (CARs). ACT offers advantages over other immunotherapies by allowing the in vitro expansion of antitumor T cells, which can then be administered to patients. The use of lymphodepletion before cell transfer enhances the effectiveness of ACT by creating a favorable microenvironment for antitumor immunity. ACT has been effective in treating metastatic melanoma, with TILs (tumor-infiltrating lymphocytes) showing durable and complete regressions in some patients. The success of ACT depends on identifying antigens expressed exclusively on cancer cells. TILs derived from melanoma tumors have been shown to recognize mutations in cancer cells, leading to tumor regression. This approach has also been applied to other cancers, such as cholangiocarcinoma, where TILs targeting specific mutations led to significant tumor regression. Genetic engineering of lymphocytes has enabled the development of CARs, which can recognize cancer-specific antigens. CARs have been successfully used to treat B cell malignancies, such as lymphoma and leukemia. However, targeting antigens shared between tumors and normal tissues can lead to severe toxicity. Despite these challenges, ACT remains a promising treatment for cancer, with ongoing research aimed at improving its safety and efficacy. The future of ACT depends on identifying suitable targets for immunologic attack and developing more effective and safer therapies.Adoptive cell therapy (ACT) is a personalized cancer immunotherapy that involves transferring immune cells with direct anticancer activity into cancer patients. This approach has shown success in treating melanoma by using tumor-reactive lymphocytes that target somatic mutations unique to each cancer. ACT has been expanded to treat common epithelial cancers through genetic engineering of lymphocytes to express T cell receptors (TCRs) or chimeric antigen receptors (CARs). ACT offers advantages over other immunotherapies by allowing the in vitro expansion of antitumor T cells, which can then be administered to patients. The use of lymphodepletion before cell transfer enhances the effectiveness of ACT by creating a favorable microenvironment for antitumor immunity. ACT has been effective in treating metastatic melanoma, with TILs (tumor-infiltrating lymphocytes) showing durable and complete regressions in some patients. The success of ACT depends on identifying antigens expressed exclusively on cancer cells. TILs derived from melanoma tumors have been shown to recognize mutations in cancer cells, leading to tumor regression. This approach has also been applied to other cancers, such as cholangiocarcinoma, where TILs targeting specific mutations led to significant tumor regression. Genetic engineering of lymphocytes has enabled the development of CARs, which can recognize cancer-specific antigens. CARs have been successfully used to treat B cell malignancies, such as lymphoma and leukemia. However, targeting antigens shared between tumors and normal tissues can lead to severe toxicity. Despite these challenges, ACT remains a promising treatment for cancer, with ongoing research aimed at improving its safety and efficacy. The future of ACT depends on identifying suitable targets for immunologic attack and developing more effective and safer therapies.