T cell therapies are still hindered by poor T cell persistence and function, making them largely ineffective against solid tumors. Human cancerous T cells acquire mutations that increase their fitness and evade immune challenges in similar situations to those faced by therapeutic T cells. Writing in Nature, Garcia and colleagues exploit the fitness-enhancing abilities of these cancer mutations by incorporating them into engineered therapeutic T cells for improved performance.
The authors screened 71 cancerous T cells mutations for their potential effect on therapeutic T cell function. Among these candidates, they identified a gene fusion, CARD11–PIK3R3, that significantly improved anti-tumor activity of T cell therapies in mouse models bearing various cancers, including melanoma. CARD11–PIK3R3 improved the efficacy of both T cell receptor (TCR) and chimeric antigen receptor (CAR)-T cell therapy by amplifying signaling through CBM, a complex that is essential for T cell activation and function in response to antigens. The mutated T cells also improved general treatment conditions, requiring lower dosing and eliminating the need for lymphodepletion chemotherapy — a procedure that is often used to improve T cell therapy effectiveness but is associated with substantial toxicities.
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
24,99 € / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
209,00 € per year
only 17,42 € per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Log in
Learn about institutional subscriptions
Read our FAQs
Contact customer support
About this article
Cite this article
Marchal, I. Supercharging T cell therapy with cancer mutations.
Nat Biotechnol42, 379 (2024). https://doi.org/10.1038/s41587-024-02184-5
Download citation
Published: 15 March 2024
Issue Date: March 2024
DOI: https://doi.org/10.1038/s41587-024-02184-5
>>> Read full article>>>
Copyright for syndicated content belongs to the linked Source : Nature.com – https://www.nature.com/articles/s41587-024-02184-5