Elsevier

Annals of Oncology

Volume 32, Issue 11, November 2021, Pages 1366-1380
Annals of Oncology

Review
Early-phenotype CAR-T cells for the treatment of pediatric cancers

https://doi.org/10.1016/j.annonc.2021.07.018Get rights and content
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Highlights

  • Early-phenotype CAR-T cells in the good manufacturing practice product are associated with improved CAR-T-cell persistence and clinical outcome in acute lymphoblastic leukemia.

  • Children have a high frequency of naïve T cells, which are an optimal source for generation of early-phenotype CAR-T cells.

  • Early CAR-T cells can be generated using memory cytokines, inhibitors, or genetic modification of T-cell signaling pathways.

  • Protocols to prevent CAR tonic signaling are also key to generate early-phenotype CAR-T cells.

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 naïve 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.

Key words

pediatric cancer
chimeric antigen receptor
T-cell memory

Cited by (0)

These authors contributed equally as first authors.

These authors contributed equally as senior authors.