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Disinhibition of Early T cell Activation via CD5 Knock Out Enhances the Anti-Tumor Activity of Adoptive T Cell Therapies

GSE248590 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/07/18 Platform GPL24676
Summary
The majority of patients treated with currently approved adoptive T-cell therapies (ACT) and, specifically, chimeric antigen receptor (CAR) T cells will eventually fail treatment. Furthermore, ACT has not been successful against solid cancers and several hematological malignancies, including T-cell lymphomas which have extremely poor prognosis. One of the main barriers to the effective activity of adoptively transferred T cells is their inhibition when they reach the tumor bed. In this study, we discover that CD5 inhibits CAR T activation and that the knockout (KO) of CD5 using CRISPR-Cas9 enhances the anti-tumor effect of CAR and TCR T cells in multiple hematological and solid cancer models. As a consequence, CD5 KO T cells display increased in vivo expansion and persistence. Despite this increased activity, no clear increased toxicity was observed in preclinical models. These findings support the development of CD5 KO adoptive T-cell therapies in early-phase clinical trials for relapsed and refractory cancer.
Published in
CD5 deletion enhances the antitumor activity of adoptive T cell therapies
Patel RP, Ghilardi G, Zhang Y et al. · Science immunology 2024 · PMID 39028827 · doi:10.1126/sciimmunol.adn6509
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Also filed as BioProject PRJNA1044818 and SRA study SRP474057. Searching any of these in the dataset finder brings you back here.

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