Next Generation Natural Killer Cells for Cancer Immunotherapy. 2022

Fiorella Rossi, and Nathaniel Fredericks, and Andrew Snowden, and Michael J Allegrezza, and Uriel Y Moreno-Nieves
Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, United States.

In recent years, immunotherapy for cancer has become mainstream with several products now authorized for therapeutic use in the clinic and are becoming the standard of care for some malignancies. Chimeric antigen receptor (CAR)-T cell therapies have demonstrated substantial efficacy for the treatment of hematological malignancies; however, they are complex and currently expensive to manufacture, and they can generate life-threatening adverse events such as cytokine release syndrome (CRS). The limitations of current CAR-T cells therapies have spurred an interest in alternative immunotherapy approaches with safer risk profiles and with less restrictive manufacturing constraints. Natural killer (NK) cells are a population of immune effector cells with potent anti-viral and anti-tumor activity; they have the capacity to swiftly recognize and kill cancer cells without the need of prior stimulation. Although NK cells are naturally equipped with cytotoxic potential, a growing body of evidence shows the added benefit of engineering them to better target tumor cells, persist longer in the host, and be fitter to resist the hostile tumor microenvironment (TME). NK-cell-based immunotherapies allow for the development of allogeneic off-the-shelf products, which have the potential to be less expensive and readily available for patients in need. In this review, we will focus on the advances in the development of engineering of NK cells for cancer immunotherapy. We will discuss the sourcing of NK cells, the technologies available to engineer NK cells, current clinical trials utilizing engineered NK cells, advances on the engineering of receptors adapted for NK cells, and stealth approaches to avoid recipient immune responses. We will conclude with comments regarding the next generation of NK cell products, i.e., armored NK cells with enhanced functionality, fitness, tumor-infiltration potential, and with the ability to overcome tumor heterogeneity and immune evasion.

UI MeSH Term Description Entries
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D007694 Killer Cells, Natural Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016219 Immunotherapy, Adoptive Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314) Adoptive Cellular Immunotherapy,Adoptive Immunotherapy,CAR T-Cell Therapy,Cellular Immunotherapy, Adoptive,Chimeric Antigen Receptor Therapy,Immunotherapy, Adoptive Cellular,Adoptive Cellular Immunotherapies,Adoptive Immunotherapies,CAR T Cell Therapy,CAR T-Cell Therapies,Cellular Immunotherapies, Adoptive,Immunotherapies, Adoptive,Immunotherapies, Adoptive Cellular,T-Cell Therapies, CAR,T-Cell Therapy, CAR,Therapies, CAR T-Cell,Therapy, CAR T-Cell
D059016 Tumor Microenvironment The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth. Cancer Microenvironment,Cancer Microenvironments,Microenvironment, Cancer,Microenvironment, Tumor,Microenvironments, Cancer,Microenvironments, Tumor,Tumor Microenvironments
D019337 Hematologic Neoplasms Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES. Blood Cancer,Hematologic Malignancies,Hematopoietic Neoplasms,Hematologic Malignancy,Hematological Malignancies,Hematological Neoplasms,Hematopoietic Malignancies,Malignancies, Hematologic,Malignancy, Hematologic,Neoplasms, Hematologic,Neoplasms, Hematopoietic,Blood Cancers,Cancer, Blood,Hematologic Neoplasm,Hematological Malignancy,Hematological Neoplasm,Hematopoietic Malignancy,Hematopoietic Neoplasm,Malignancy, Hematological,Malignancy, Hematopoietic,Neoplasm, Hematologic,Neoplasm, Hematological,Neoplasm, Hematopoietic

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