Engineering the next generation of CAR-NK immunotherapies
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 C...
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| Veröffentlicht in: | International journal of hematology 2021-11, Vol.114 (5), p.554-571 |
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| container_title | International journal of hematology |
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| creator | Biederstädt, Alexander Rezvani, Katayoun |
| description | 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. |
| doi_str_mv | 10.1007/s12185-021-03209-4 |
| format | Article |
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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. 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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. 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| ispartof | International journal of hematology, 2021-11, Vol.114 (5), p.554-571 |
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| subjects | Animals Biocompatibility Blood cancer CD19 antigen Cell therapy Clinical Trials as Topic Combined Modality Therapy CRISPR Disease Management Disease Susceptibility Gene Editing Genetic engineering Genetic Engineering - methods Genetic Therapy Hematologic Neoplasms - diagnosis Hematologic Neoplasms - etiology Hematologic Neoplasms - therapy Hematology Humans Immune system Immunotherapy Immunotherapy, Adoptive - adverse effects Immunotherapy, Adoptive - methods Immunotherapy, Adoptive - trends Innate immunity Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Lymphocytes Lymphocytes T Medicine Medicine & Public Health Metabolism Natural killer cells Oncology Progress in Hematology Receptors, Chimeric Antigen - immunology Solid tumors Toxicity Translational Research, Biomedical Treatment Outcome |
| title | Engineering the next generation of CAR-NK immunotherapies |
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