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Review
. 2021 Aug 6:11:720501.
doi: 10.3389/fonc.2021.720501. eCollection 2021.

From CAR-T Cells to CAR-NK Cells: A Developing Immunotherapy Method for Hematological Malignancies

Hui Lu  1 , Xiaoyan Zhao  1 , Ziying Li  1 , Yu Hu  1 , Huafang Wang  1
Affiliations
Review

From CAR-T Cells to CAR-NK Cells: A Developing Immunotherapy Method for Hematological Malignancies

Hui Lu et al. Front Oncol. .

Abstract

The approval of CD19 chimeric antigen receptor (CAR)-engineered T (CAR-T) cell products in B-cell malignancies represents a breakthrough in CAR-T cell immunotherapy. However, the remaining limitations concerning the graft-versus-host disease (GVHD) and other adverse effects (e.g., cytokine release syndromes [CRS] and neurotoxicity) still restrict their wider applications. Natural killer (NK) cells have been identified as promising candidates for CAR-based cellular immunotherapy because of their unique characteristics. No HLA-matching restriction and abundant sources make CAR-engineered NK (CAR-NK) cells potentially available to be off-the-shelf products that could be readily available for immediate clinical use. Therefore, researchers have gradually shifted their focus from CAR-T cells to CAR-NK cells in hematological malignancies. This review discusses the current status and applications of CAR-NK cells in hematological malignancies, as well as the unique advantages of CAR-NK cells compared with CAR-T cells. It also discusses challenges and prospects regarding clinical applications of CAR-NK cells.

Keywords: T cells; chimeric antigen receptor; hematological malignancies; immunotherapy; natural killer cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The interaction between immune cells and tumor cells in tumor microenvironment. CAR-NK cells recognize and exert their killing effects through both CAR-dependent and CAR-independent manners. Different generations and types of CAR-NK cells. A CAR structure contains an extracellular binding domain (e.g., ScFv or NKG2D), a hinge region, a transmembrane domain, and one or more intracellular signaling domains.
Figure 2
Figure 2
The sources and manufacturing process of CAR-NK cells and CAR-T cells, respectively. Current sources of clinical-grade NK cells include the NK92 cell line, autologous or allogeneic PBMC-derived NK cells, UCB-derived NK cells, and iPSCs-derived NK cells. iPSCs can be genetically engineered with CAR-gene and the resulting CAR-iPSCs can be differentiated into homogeneous CAR-NK cells for clinical use. Irradiation is necessary before the infusion of CAR-NK92 cells to eliminate the potential risk of malignant transformation. At present, autologous PBMC-derived T cells are the main source of T cells for CAR-gene engineering. Allogeneic T cells from healthy donors may cause life-threatening GVHD due to HLA restriction.
See this image and copyright information in PMC

References

    1. Auberger P, Tamburini-Bonnefoy J, Puissant A. Drug Resistance in Hematological Malignancies. Int J Mol Sci (2020) 21(17):6091. 10.3390/ijms21176091 - DOI - PMC - PubMed
    1. Coller BS. Blood at 70: Its Roots in the History of Hematology and its Birth. Blood (2015) 126(24):2548–60. 10.1182/blood-2015-09-659581 - DOI - PMC - PubMed
    1. Im A, Pavletic SZ. Immunotherapy in Hematologic Malignancies: Past, Present, and Future. J Hematol Oncol (2017) 10(1):94. 10.1186/s13045-017-0453-8 - DOI - PMC - PubMed
    1. Cirillo M, Tan P, Sturm M, Cole C. Cellular Immunotherapy for Hematologic Malignancies: Beyond Bone Marrow Transplantation. Biol Blood Marrow Transplant (2018) 24(3):433–42. 10.1016/j.bbmt.2017.10.035 - DOI - PubMed
    1. Gökbuget N, Canaani J, Nagler A, Bishop M, Kröger N, Avigan D. Prevention and Treatment of Relapse After Stem Cell Transplantation With Immunotherapy. Bone Marrow Transplant (2018) 53(6):664–72. 10.1038/s41409-018-0232-3 - DOI - PubMed