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Review
. 2020 Dec 4;2020(1):570-578.
doi: 10.1182/hematology.2020002547.

Next-generation cell therapies: the emerging role of CAR-NK cells

Rafet Basar  1 , May Daher  1 , Katayoun Rezvani  1
Affiliations
Review

Next-generation cell therapies: the emerging role of CAR-NK cells

Rafet Basar et al. Hematology Am Soc Hematol Educ Program. .

Abstract

T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical, and toxicity issues. Given these concerns, there is a rapidly growing interest in natural killer cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the allogeneic setting. Other immune effector cells, such as invariant natural killer T cells, γδ T cells, and macrophages, are attracting interest as well and eventually may be added to the repertoire of engineered cell therapies against cancer. The pace of these developments will undoubtedly benefit from multiple innovative technologies, such as the CRISPR-Cas gene editing system, which offers great potential to enhance the natural ability of immune effector cells to eliminate refractory cancers.

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Conflict of interest statement

Conflict-of-interest disclosure: K.R., M.D., R.B., and The University of Texas MD Anderson Cancer Center (MDACC) have an institutional financial conflict of interest with Takeda Pharmaceutical for the licensing of the technology related to the research mentioned here. MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to MDACC’s conduct of any other ongoing or future research related to this relationship.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
NK cell repertoire of activating and inhibitory receptors. AR, activating receptor; BAG6, BCL2-associated athanogene 6; DAP10, DNAX activating protein of 12 KDa; DAP12, DNAX activating protein of 12 KDa; DNAM1, DNAX accessory molecule 1; GAGs, glycosaminoglycans; Gal-9, galectin-9; HA, hemagglutinin; HS, heparan sulfate; IR, inhibitory receptor; ITAM, immunoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-based activation motif; ITSM, immunoreceptor tyrosine-based switch motif; ITT-like, immunoglobulin tail tyrosine-like; KIR, killer immunoglobulin like receptor; KLRG1, killer cell lectin-like receptor G1; LAIR1, leukocyte-associated immunoglobulin like receptor-1; LILRB1, leukocyte Ig-like receptor B1; MIC-A/B, MHC class I chain-related proteins A and B; PD1, programmed cell death protein 1; PDL-1, programmed cell death ligand 1; PDL-2, programmed cell death ligand 2; TIGIT, T-cell immunoreceptor with Ig and ITIM domains; TIM3, T-cell immunoglobulin mucin domain-3; YXXM, Y stands for tyrosine, X for any amino acid residue, and M for methionine.
See this image and copyright information in PMC

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