CAR-NK cells for cancer immunotherapy: from bench to bedside

Zhang, Leisheng; Yuan, Meng; Feng, Xiaoming; Han, Zhongchao

doi:10.1186/s40364-022-00364-6

Cited by 114 publications

(90 citation statements)

References 164 publications

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“…The most common sources used as platforms to develop CAR-NK therapy are NK cells from peripheral blood (PB) or UCB, NK cell lines (such as NK92), and stem cell-derived NK cells, generated from iPSCs, human embryonic stem cells (hESCs) or CD34 + hematopoietic stem cells ( 39 ). PB-NK cells are mature cells with high cytotoxic activity and extended expansion potential but show challenges regarding genetic modification.…”

Section: Manufacturing Conditions: Key Aspect For the Efficacy Of Car...mentioning

confidence: 99%

Overcoming tumor resistance mechanisms in CAR-NK cell therapy

et al. 2022

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Despite the impressive results of autologous CAR-T cell therapy in refractory B lymphoproliferative diseases, CAR-NK immunotherapy emerges as a safer, faster, and cost-effective approach with no signs of severe toxicities as described for CAR-T cells. Permanently scrutinized for its efficacy, recent promising data in CAR-NK clinical trials point out the achievement of deep, high-quality responses, thus confirming its potential clinical use. Although CAR-NK cell therapy is not significantly affected by the loss or downregulation of its CAR tumor target, as in the case of CAR-T cell, a plethora of common additional tumor intrinsic or extrinsic mechanisms that could also disable NK cell function have been described. Therefore, considering lessons learned from CAR-T cell therapy, the emergence of CAR-NK cell therapy resistance can also be envisioned. In this review we highlight the processes that could be involved in its development, focusing on cytokine addiction and potential fratricide during manufacturing, poor tumor trafficking, exhaustion within the tumor microenvironment (TME), and NK cell short in vivo persistence on account of the limited expansion, replicative senescence, and rejection by patient’s immune system after lymphodepletion recovery. Finally, we outline new actively explored alternatives to overcome these resistance mechanisms, with a special emphasis on CRISPR/Cas9 mediated genetic engineering approaches, a promising platform to optimize CAR-NK cell function to eradicate refractory cancers.

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Section: Manufacturing Conditions: Key Aspect For the Efficacy Of Car...mentioning

confidence: 99%

Overcoming tumor resistance mechanisms in CAR-NK cell therapy

et al. 2022

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“…CAR NK cells were developed as an alternative to CAR T cell therapies to address some of the potential issues present in CAR T cell therapies. The first CAR NK clinical trials began in 2016, and currently there are 32 CAR NK cell therapies in clinical trials, with many of them aimed at targeting blood cancers through BCMA and CD19 antigen-targeting [ 109 , 115 , 116 ]. Currently, CAR NK cells are a viable option for cancer immunotherapy development but face challenges in ex vivo cell expansion, storage conditions, and optimal cellular cytotoxicity.…”

Section: Car Nk Cellsmentioning

confidence: 99%

Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer

et al. 2022

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For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs. Other immune cell types, including natural killer (NK) cells and macrophages, have also been engineered to express CARs to treat cancer. Additionally, CAR technology has been adapted in novel approaches to treating autoimmune disease and other conditions and diseases. In this article, we review these recent advancements in alternative CAR therapies and design, as well as their mechanisms of action, challenges in application, and potential future directions.

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“…Moreover, immunotherapy based on NKs displayed several advantages ( 147 , 148 ). As the important immune system components, NKs exerted the cytotoxicity upon recognizing specific patterns without prior antigen sensitization.…”

Section: Nk Cell-based Immunotherapymentioning

confidence: 99%

Immunotherapy for Pediatric Acute Lymphoblastic Leukemia: Recent Advances and Future Perspectives

Liu

et al. 2022

Front. Immunol.

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Pediatric acute lymphoblastic leukemia (ALL) is the most common subtype of childhood leukemia, which is characterized by the abnormal proliferation and accumulation of immature lymphoid cell in the bone marrow. Although the long-term survival rate for pediatric ALL has made significant progress over years with the development of contemporary therapeutic regimens, patients are still suffered from relapse, leading to an unsatisfactory outcome. Since the immune system played an important role in the progression and relapse of ALL, immunotherapy including bispecific T-cell engagers and chimeric antigen receptor T cells has been demonstrated to be capable of enhancing the immune response in pediatric patients with refractory or relapsed B-cell ALL, and improving the cure rate of the disease and patients’ quality of life, thus receiving the authorization for market. Nevertheless, the resistance and toxicities associated with the current immunotherapy remains a huge challenge. Novel therapeutic options to overcome the above disadvantages should be further explored. In this review, we will thoroughly discuss the emerging immunotherapeutics for the treatment of pediatric ALL, as well as side-effects and new development.

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CAR-NK cells for cancer immunotherapy: from bench to bedside

Cited by 114 publications

References 164 publications

Overcoming tumor resistance mechanisms in CAR-NK cell therapy

Overcoming tumor resistance mechanisms in CAR-NK cell therapy

Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer

Immunotherapy for Pediatric Acute Lymphoblastic Leukemia: Recent Advances and Future Perspectives

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