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The identification of melanoma-associated antigens, the isolation of tumor infiltrating T cells from melanoma lesions, and the significant progress in engineering redirected T cells has favored the development of various strategies in the adoptive immunotherapy of mel‐ anoma. Recent trials in adoptive cell therapy (ACT) have achieved spectacular results in inducing remission in advanced stages of the disease, although produced on-target off-tu‐ mor toxicities, emphasizing the tremendous potential benefit of harnessing the immune system for fighting the disease. Moreover, the identification of so-called melanoma stem cells along with strategies for selectively eliminating subsets of melanoma cells implies that there is a need for redefining therapeutic targets in melanoma. This review discusses current challenges in the rational design of adoptive cell therapy to target “the beating heart” of melanoma.

Adoptive Cell Therapy of Melanoma: The Challenges of Targeting the Beating Heart