Cellular networks controlling T cell persistence in adoptive cell therapy
- Author(s)
- Chan, JD; Lai, J; Slaney, CY; Kallies, A; Beavis, PA; Darcy, PK;
- Details
- Publication Year 2021-12,Volume 21,Issue #12,Page 769-784
- Journal Title
- Nature Reviews Immunology
- Publication Type
- Review
- Abstract
- The antitumour activity of endogenous or adoptively transferred tumour-specific T cells is highly dependent on their differentiation status. It is now apparent that less differentiated T cells compared with fully differentiated effector T cells have better antitumour therapeutic effects owing to their enhanced capacity to expand and their long-term persistence. In patients with cancer, the presence of endogenous or adoptively transferred T cells with stem-like memory or precursor phenotype correlates with improved therapeutic outcomes. Advances in our understanding of T cell differentiation states at the epigenetic and transcriptional levels have led to the development of novel methods to generate tumour-specific T cells - namely, chimeric antigen receptor T cells - that are more persistent and resistant to the development of dysfunction. These include the use of novel culture methods before infusion, modulation of transcriptional, metabolic and/or epigenetic programming, and strategies that fine-tune antigen receptor signalling. This Review discusses existing barriers and strategies to overcome them for successful T cell expansion and persistence in the context of adoptive T cell immunotherapy for solid cancers.
- Keywords
- Animals; Cell- and Tissue-Based Therapy; Humans; *Immunotherapy, Adoptive; Lymphocyte Activation; Neoplasms/*immunology/pathology/*therapy; T-Lymphocytes/*cytology/*immunology
- Department(s)
- Laboratory Research
- PubMed ID
- 33879873
- Publisher's Version
- https://doi.org/10.1038/s41577-021-00539-6
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-06-20 08:03:13
Last Modified: 2025-06-20 08:04:25