期刊
ANNALS OF ONCOLOGY
卷 32, 期 11, 页码 1366-1380出版社
ELSEVIER
DOI: 10.1016/j.annonc.2021.07.018
关键词
pediatric cancer; chimeric antigen receptor; T-cell memory
类别
资金
- Medical Research Future Fund Australian Brain Cancer Mission
- National Health and Medical Research Council program grant (NHMRC) [1132373]
- Fondation Nuovo Soldati
- Fondation de France
- Movember PCRA grant
- Tour de Cure Pioneering Research Grant
- Austra-lian and New Zealand Sarcoma Association, and Xavier Kri-kori Sarcoma Research Grant
- NHMRC program grant
- Samuel Nissen Charitable Foundation
- National Health and Medical Research Council of Australia [1132373] Funding Source: NHMRC
CAR-T therapy shows promise for treating childhood cancers, especially when maintained in an early phenotypic stage. Early CAR-T cells have shown superior persistence, proliferation, and antitumor effects, particularly relevant for pediatric patients.
Chimeric antigen receptor (CAR)-T-cell therapy is a promising approach for the treatment of childhood cancers, particularly high-risk tumors that fail to respond to standard therapies. CAR-T cells have been highly successful in treating some types of hematological malignancies. However, CAR-T cells targeting solid cancers have had limited success so far for multiple reasons, including their poor long-term persistence and proliferation. Evidence is emerging to show that maintaining CAR-T cells in an early, less-differentiated state in vitro results in superior persistence, proliferation, and antitumor effects in vivo. Children are ideal candidates for receiving less-differentiated CAR-T cells, because their peripheral T-cell pool primarily comprises naive cells that could readily be harvested in large numbers to generate early-phenotype CAR-T cells. Although several studies have reported different approaches to successfully generate early CAR-T cells, there are only a few clinical trials testing these in adult patients. No trials are currently testing early CAR-T cells in children. Here, we summarize the different strategies used to maintain CAR-T cells in an early phenotypic stage and present evidence suggesting that this approach may be particularly relevant to treating childhood cancers.
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