In patients, poor persistence and function of adoptively transferred cells are major obstacles for T cell-based tumor therapies. St. Jude researchers demonstrated that by knocking out REGNASE-1, which is identified in an in vivo CRISPR discovery platform, CD8 T cell long-term persistence is greatly improved (up to 2000x), and these cells are resistant to functional exhaustion and retain robust effector function. Strikingly, REGNASE-1 deficient CD8 T cells have greatly improved ability in controlling both solid and blood cancers; making it useful in engineered T cell, including CAR-T cell, based tumor immune therapy, and potentially, regulatory T cell (Treg) based immune therapy in autoimmune diseases. Additional factors were identified to act alone or in combination with REGNASE-1 deletion to improve T-cell function.
The researchers also discovered that by overexpressing one single molecular (BATF; Basic Leucine Zipper ATF-Like Transcription Factor), the accumulation and effector function of tumor-specific T cells are markedly enhanced. This is useful for immunotherapy against solid and blood cancers using CAR-T and other engineered T cells.
adoptive T cell cancer therapy, CAR-T, REGNASE-1, Basic Leucine Zipper ATF-Like Transcription Factor (BATF), long-term persistence, effector function, solid tumor, blood cancer, autoimmune diseases, CRISPR
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The paper is online now. https://www.nature.com/articles/s41586-019-1821-z
It is also selected by News and Views in Nature https://www.nature.com/articles/d41586-019-03731-w
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