Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors
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Natural killer (NK) cells, key antitumor effectors of the innateimmune system, are endowed with the unique ability to spontaneouslyeliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types ofcancer and close association with cancer prognosis, NK cellshave gained considerable attention as a promising therapeutictarget for cancer immunotherapy. NK cell-based therapies havedemonstrated favorable clinical efficacies in several hematologicalmalignancies but limited success in solid tumors, thushighlighting the need to develop new therapeutic strategies torestore and optimize anti-tumor activity while preventing tumorimmune escape. The current therapeutic modalities yieldingencouraging results in clinical trials include the blockade of immunecheckpoint receptors to overcome the immune-evasionmechanism used by tumors and the incorporation of tumor-directedchimeric antigen receptors to enhance NK cell anti-tumorspecificity and activity. These observations, together with recentadvances in the understanding of NK cell activation within thetumor microenvironment, will facilitate the optimal design ofNK cell-based therapy against a broad range of cancers and,more desirably, refractory cancers.
Abstract
Natural killer (NK) cells, key antitumor effectors of the innateimmune system, are endowed with the unique ability to spontaneouslyeliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types ofcancer and close association with cancer prognosis, NK cellshave gained considerable attention as a promising therapeutictarget for cancer immunotherapy. NK cell-based therapies havedemonstrated favorable clinical efficacies in several hematologicalmalignancies but limited success in solid tumors, thushighlighting the need to develop new therapeutic strategies torestore and optimize anti-tumor activity while preventing tumorimmune escape. The current therapeutic modalities yieldingencouraging results in clinical trials include the blockade of immunecheckpoint receptors to overcome the immune-evasionmechanism used by tumors and the incorporation of tumor-directedchimeric antigen receptors to enhance NK cell anti-tumorspecificity and activity. These observations, together with recentadvances in the understanding of NK cell activation within thetumor microenvironment, will facilitate the optimal design ofNK cell-based therapy against a broad range of cancers and,more desirably, refractory cancers.
참고문헌 (141)
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