Gene-edited and CAR-NK cells: Opportunities and challenges with engineering of NK cells for immunotherapy

Wang, Xinyu; Matosevic, Sandro

doi:10.1016/j.omto.2022.10.011

Cited by 8 publications

(3 citation statements)

References 159 publications

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“…They also regulate cancer cell death by patterned recognition of target ligands [ 90 , 91 ]. CAR-T cells can only target tumor cells using specific antibodies against scFv, whereas NK cells can be widely activated through their activating and inhibitory receptors [ 92 ]. The balance between activating and inhibitory receptors in NK cells is important for regulating their cytotoxic activity.…”

Section: Car-nk Cell Therapymentioning

confidence: 99%

Recent Advances in CAR-Based Solid Tumor Immunotherapy

Shin¹,

Oh²,

Kim³

et al. 2023

Cells

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Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design—such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells—have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.

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Section: Car-nk Cell Therapymentioning

confidence: 99%

Recent Advances in CAR-Based Solid Tumor Immunotherapy

Shin¹,

Oh²,

Kim³

et al. 2023

Cells

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“…15 CAR-NK cells have also shown remarkable results for different cancer treatments. 16 However, due to the limitations of CAR modification, 17 different alternative nongenetic approaches have been explored, including, antibody, 18 nanobody, 19 lipid-aptamer, 20 antibody−drug conjugates, 21 etc., for the NK cell surface modification. However, NK cells for HCC treatment can be deactivated by NK-HCC cell interaction (NKp30 and MSDCs on HCC) resulting in failure of penetration into the solid tumor tissues.…”

Section: Introductionmentioning

confidence: 99%

Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma

Jangid,

Kim,

Kim

et al. 2023

Bioconjugate Chem.

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Natural killer (NK) cells exhibit a good therapeutic efficacy against various malignant cancer cells. However, the therapeutic efficacy of plain NK cells is relatively low due to inadequate selectivity for cancer cells. Therefore, to enhance the targeting selectivity and anticancer efficacy of NK cells, we have rationally designed a biomaterial-mediated ex vivo surface engineering technique for the membrane decoration of cancer recognition ligands onto NK cells. Our designed lipid conjugate biomaterial contains three major functional moieties: (1) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid for cell membrane anchoring, (2) polyethylene glycol for intracellular penetration blocker, and (3) lactobionic acid (LBA) for cancer recognition. The biomaterial was successfully applied to NK cell surfaces (LBA-NK) to enhance recognition and anticancer functionalities, especially toward asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma. Highly efficient and homogeneous NK cell surface editing was achieved with a simple coating process while maintaining intrinsic properties of NK cells. LBA-NK cells showed potential ASGPR-mediated tumor cell binding (through LBA-ASGPR interaction) and thereby significantly augmented anticancer efficacies against HepG2 liver cancer cells. Thus, LBA-NK cells can be a novel engineering strategy for the treatment of liver cancers via facilitated immune synapse interactions in comparison with currently available cell therapies.

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“…However, more therapeutic precision is still required to target tumors accurately. Moreover, multiplexed precision genome editing with pros and cons has become a highly flexible and modular toolkit for specifically addressing the challenges of precision interventions ( 35 – 37 ). Towards better functionality, genome editing tools like CRISPR/Cas9 and TALENs have made it possible to create additional genetic modifications in immune cells ( 36 , 38 , 39 ).…”

mentioning

confidence: 99%