Targeting Natural Killer Cells for Tumor Immunotherapy.

Frontiers in Immunology
Cai ZhangChongdeng Shi

Abstract

Natural killer (NK) cells are important innate cytotoxic lymphocytes with a rapid and efficient capacity to recognize and kill tumor cells. In recent years, adoptive transfer of autologous- or allogeneic-activated NK cells has become a promising cellular therapy for cancer. However, the therapeutic efficiency is encouraging in hematopoietic malignancies, but disappointing in solid tumors, for which the use of NK-cell-based therapies presents considerable challenges. It is difficult for NK cells to traffic to, and infiltrate into, tumor sites. NK cell function, phenotype, activation, and persistence are impaired by the tumor microenvironment, even leading to NK cell dysfunction or exhaustion. Many strategies focusing on improving NK cells' durable persistence, activation, and cytolytic activity, including activation with cytokines or analogs, have been attempted. Modifying them with chimeric antigen receptors further increases the targeting specificity of NK cells. Checkpoint blockades can relieve the exhausted state of NK cells. In this review, we discuss how the cytolytic and effector functions of NK cells are affected by the tumor microenvironment and summarize the various immunotherapeutic strategies based on NK cells. In pa...Continue Reading

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Citations

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Methods Mentioned

BETA
transfection
xenograft
glycosylation

Clinical Trials Mentioned

NCT01885897
NCT01946789
NCT02099539
NCT03054909
NCT02465957
NCT02890758
NCT02523469
NCT03068819
NCT02782546
NCT01898793

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