Immunotherapy for metastatic solid cancers.

After decades of research on solid tumor immunology, immunotherapy has shown effectiveness in patients with metastatic solid cancers. Immune modulators such as IL-2 and anti-CTLA-4 can mediate tumor regression in patients with metastatic melanoma and renal cancer, two tumor types that appear exceptional in their ability to spontaneously harbor endogenous antitumor immune cells. The responses can be long lasting, but the number of patients who benefit from these molecules remains limited. Combinations of these agents with cytotoxic and biologic agents are being investigated as a means to increase response rates and in an attempt to broaden application to other cancer types. Rare responses to cancer vaccines suggest that a better understanding of the underlying biology and mechanism of actions may lead to wider application in the future. The most effective form of immunotherapy thus far, capable of eradicating large tumor burdens in melanoma patients, is the ACT of TIL given to patients after lymphodepletion. As an alternative, lymphocytes engineered to recognize tumor-associated antigens can be safely infused to patients. With this approach, tumor regression is now being reported for cancers other than melanoma, but success remains constrained by the identification of antigens expressed with high specificity by cancer cells and not by normal tissues.