Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors

Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recur...

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Bibliographic Details
Published in:Cancers 2021-06, Vol.13 (11), p.2796
Main Authors: Quamine, Aicha E., Olsen, Mallery R., Cho, Monica M., Capitini, Christian M.
Format: Article
Language:English
Subjects:
Adapter proteins
Antigens
Antitumor activity
Bone cancer
Cancer
Cell therapy
Chemotherapy
Children
Chimeric antigen receptors
Clinical trials
Cytokines
Cytotoxicity
Effector cells
Graft-versus-host reaction
Growth factors
Immune system
Immunotherapy
Kinases
Leukemia
Licenses
Ligands
Lymphocytes
Lymphoma
Major histocompatibility complex
Metastases
Natural killer cells
Neuroblastoma
Patients
Pediatrics
Phosphatase
Review
Solid tumors
Stem cells
Tumors
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Summary:Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become refractory to prior therapy, leaving patients with few conventional treatment options. Natural killer (NK) cells are non-major histocompatibility complex (MHC)-restricted lymphocytes that boast several complex killing mechanisms but at an added advantage of not causing graft-versus-host disease, making use of allogeneic NK cells a potential therapeutic option. On top of their killing capacity, NK cells also produce several cytokines and growth factors that act as key regulators of the adaptive immune system, positioning themselves as ideal effector cells for stimulating heavily pretreated immune systems. Despite this promise, clinical efficacy of adoptive NK cell therapy to date has been inconsistent, prompting a detailed understanding of the biological pathways within NK cells that can be leveraged to develop “next generation” NK cell therapies. Here, we review advances in current approaches to optimizing the NK cell antitumor response including combination with other immunotherapies, cytokines, checkpoint inhibition, and engineering NK cells with chimeric antigen receptors (CARs) for the treatment of pediatric solid tumors.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13112796