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New horizons in target antigen selection in adoptive cell therapy of cancer
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Abstract:
Adoptive cell transfer (ACT) is a passive immunotherapy of cancer. Recently, researchers have observed that durable complete cancer regressions can be achieved in patients with metastatic melanoma after ACT, encouragingly suggesting a great potential for ACT in the treatment of cancer in clinical settings. This potential can be further enhanced when genetic modification of lymphocytes is performed. The key to the success of adoptive cell therapy is the identification of suitable immunologic targets on cancer cells that can be attacked by tumor infiltrating lymphocytes (TIL) or genetically modified lymphocytes without damaging normal tissues. Differentiation antigens overexpressed on cancers, shared non-mutated antigens of cancers, and antigens from tumor stroma are not suitable targets of ACT due to their low level expression in normal tissues. On the contrary, antigens encoded by shared mutations, viral oncogenes, or unique driver mutations may serve as ideal targets of ACT. Further development of ACT will result from new adoptive cell immunotherapy strategies with lymphocytes that recognize mutated antigens, in particular those derived from gene products that are involved in carcinogenesis.
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Project Supported:
Project supported by the Key Technologies R&D Program of China (No. 2015BAI12B12), and the Tianjin Application Foundation and Advanced Technology Research Prgram (No.13JCYBJC41400, No.14JCTPJC00476)
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