Engineering Natural Killer Cells for Cancer Immunotherapy.

Abstract

The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification. We will discuss strategies to introduce CARs into both primary NK cells and NK cell lines in an effort to provide antigen specificity, the challenges of manufacturing engineered NK cells, and evidence supporting the effectiveness of this approach from preclinical and early-phase clinical studies using CAR-engineered NK cells. CAR-NK cells hold great promise as a novel cellular immunotherapy against refractory malignancies. Notably, NK cells can provide an "off-the-shelf" product, eliminating the need for a personalized and patient-specific product that plagues current CAR-T cell therapies. The ability to more potently direct NK cell-mediated cytotoxicity against refractory tumors through the expression of CAR is likely to contribute to the recent paradigm shift in cancer treatment.

• Authors: Katayoun Rezvani, Rayne Rouce, Enli Liu, Elizabeth Shpall
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 25 Issue 8 Pg. 1769-1781 (08 02 2017) ISSN: 1525-0024 [Electronic] United States
• PMID: 28668320 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Receptors, Antigen, T-Cell

Topics

• Animals
• Biomarkers
• Cell- and Tissue-Based Therapy (methods)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Genetic Engineering (methods)
• Humans
• Immunotherapy, Adoptive (adverse effects, methods)
• Killer Cells, Natural (cytology, immunology, metabolism)
• Neoplasms (immunology, therapy)
• Receptors, Antigen, T-Cell (genetics, metabolism)
• Signal Transduction
• T-Lymphocytes (immunology, metabolism)
• Translational Research, Biomedical