期刊
INTERNATIONAL JOURNAL OF HEMATOLOGY
卷 114, 期 5, 页码 554-571出版社
SPRINGER JAPAN KK
DOI: 10.1007/s12185-021-03209-4
关键词
Chimeric antigen receptor; Cellular immunotherapy; Natural killer cells; Genetic engineering; Metabolic reprogramming
类别
资金
- German Research Foundation as Walter Benjamin Postdoctoral Fellow
- Lyda Hill Philanthropies
- University of Texas MD Anderson Cancer Center Moon Shots Program
- CPRIT [RP160693]
- Stand Up To Cancer Dream Team Research Grant [SU2C-AACR-DT-29-19, 1 R01 CA211044-01, 5 P01CA148600-03, P50CA10063216]
- National Institutes of Health (NIH)
- Specialized Program of Research Excellence (SPORE) in Brain Cancer Grant [P50CA127001, CA016672]
- MD Anderson Cancer Center from the NIH
- American Association for Cancer Research
- scientific partner of SU2C
Cellular immunotherapy, particularly CAR-NK therapy, has shown promising efficacy in treating hematologic malignancies. Research is focused on enhancing CAR-NK cell potency and translating successful strategies to solid tumor treatments.
Over the past few years, cellular immunotherapy has emerged as a novel treatment option for certain forms of hematologic malignancies with multiple CAR-T therapies now routinely administered in the clinic. The limitations of generating an autologous cell product and the challenges of toxicity with CAR-T cells underscore the need to develop novel cell therapy products that are universal, safe, and potent. Natural killer (NK) cells are part of the innate immune system with unique advantages, including the potential for off-the-shelf therapy. A recent first-in-human trial of CD19-CAR-NK infusion in patients with relapsed/refractory lymphoid malignancies proved safe with promising clinical activity. Building on these encouraging clinical responses, research is now actively exploring ways to further enhance CAR-NK cell potency by prolonging in vivo persistence and overcoming mechanisms of functional exhaustion. Besides these strategies to modulate CAR-NK cell intrinsic properties, there are increasing efforts to translate the successes seen in hematologic malignancies to the solid tumor space. This review will provide an overview on current trends and evolving concepts to genetically engineer the next generation of CAR-NK therapies. Emphasis will be placed on innovative multiplexed engineering approaches including CRISPR/Cas9 to overcome CAR-NK functional exhaustion and reprogram immune cell metabolism for enhanced potency.
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