Back to Search
Start Over
Multi-armored allogeneic MUC1 CAR T cells enhance efficacy and safety in triple-negative breast cancer.
- Source :
-
Science Advances . 8/30/2024, Vol. 10 Issue 35, p1-21. 21p. - Publication Year :
- 2024
-
Abstract
- Solid tumors, such as triple-negative breast cancer (TNBC), are biologically complex due to cellular heterogeneity, lack of tumor-specific antigens, and an immunosuppressive tumor microenvironment (TME). These challenges restrain chimeric antigen receptor (CAR) T cell efficacy, underlining the importance of armoring. In solid cancers, a localized tumor mass allows alternative administration routes, such as intratumoral delivery with the potential to improve efficacy and safety but may compromise metastatic-site treatment. Using a multi-layered CAR T cell engineering strategy that allowed a synergy between attributes, we show enhanced cytotoxic activity of MUC1 CAR T cells armored with PD1KO, tumor-specific interleukin-12 release, and TGFBR2KO attributes catered towards the TNBC TME. Intratumoral treatment effectively reduced distant tumors, suggesting retention of antigen-recognition benefits at metastatic sites. Overall, we provide preclinical evidence of armored non-alloreactive MUC1 CAR T cells greatly reducing high TNBC tumor burden in a TGFB1-and PD-L1- rich TME both at local and distant sites while preserving safety. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TRIPLE-negative breast cancer
*CHIMERIC antigen receptors
*T cells
Subjects
Details
- Language :
- English
- ISSN :
- 23752548
- Volume :
- 10
- Issue :
- 35
- Database :
- Academic Search Index
- Journal :
- Science Advances
- Publication Type :
- Academic Journal
- Accession number :
- 179455932
- Full Text :
- https://doi.org/10.1126/sciadv.adn9857