Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors
Open accessAbstract
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.
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Loading NK cells with a CAR targeting a specific osteosarcoma antigen overcomes their limitation in recognizing tumor antigens.
“When the NK cells are loaded a CAR targeting specific osteosarcoma antigen, this limitation can be overcome [141].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [141]
Section 6 (CAR NK Cells; page unavailable) says that introducing a CAR can overcome NK cells’ limitation in recognizing tumor antigens. The paper does not establish this specifically for a CAR targeting an osteosarcoma antigen; its osteosarcoma discussion in Section 2.2 concerns antigen targeting through a different mechanism. (LLM, conf=0.87)
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Additional file 1 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056669
Additional file 7 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056687
Additional file 2 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056672
Additional file 6 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056684
Additional file 4 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056678
Additional file 5 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056681
Additional file 3 of The immune landscape of solid pediatric tumors
Sherif, S., Roelands, J. P., Mifsud, W., Ahmed, E. I., Raynaud, C. M., Rinchai, D., Sathappan, A., Maaz, A., Saleh, A., Ozer, E., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20056675
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Self-citationGene-based immunotherapy in osteosarcoma: from oncolytic vectors to engineered immune cells
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Kumari, H., Chou, C., Lee, Y.-T., Shen, C.-H., & Chan, M. W. Y. (2026) · Experimental Biology and Medicine · doi:10.3389/ebm.2026.11373
- Authors
- Quamine, A. E., Olsen, M. R., Cho, M. M., & Capitini, C. M.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Capitini, Christian M.
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2021-06-04
- Volume
- 13
- Issue
- 11
- Pages
- 2796
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8200074
- OpenAlex
- W3172210430
- Cited by
- 39
- References
- 171
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 16
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (DGE-1747503)
- National Institute of General Medical Sciences (T32 GM008692)
- National Cancer Institute (T32 CA009135, R01 CA215461)
- St. Baldrick's Foundation (SU2C-AACR-DT-27-17)
- Stand Up To Cancer (SU2C-AACR-DT-27-17)
- American Cancer Society (RSG-18-104-01-LIB)
- Midwest Athletes Against Childhood Cancer (133-PRJ55IL)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- natural killer cells, adoptive NK cell therapy, pediatric solid tumors, relapsed/refractory cancer, allogeneic NK cells, neuroblastoma, combination immunotherapy, cytokines, immune checkpoint blockade, CAR-NK cells, NK cell engineering, antitumor immunity
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