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Msg  24980 of 25208  at  9/24/2021 5:02:52 PM  by

DMtech

The following message was updated on 9/24/2021 5:08:56 PM.

MDPI - Evolution of CD8+ T Cell Receptor (TCR) Engineered Therapies for the Treatment of Cancer PDF 9/10/21

 
 Recent MDA research article.  IIRC, Rosenberg/NCI and Deniger have improved Sleeping Beauty's transduction efficiency since the cited article in 2016.  In the last paragraph (conclusion), NCI and Deniger have addressed most of the concerns listed by authors.  All the best.  
 
 
"Meanwhile, several non-viral gene editing methods have been developed. mRNA electroporation has been proven to achieve transient TCR and CAR expression, thereby minimizing the risk of viral element persistence [60–62]. Clinical data have shown that both mRNA-modified TCR-T and CAR T cells are feasible and safe without overt evidence of offtarget toxicity against normal tissues [61,62]. However, lack of persistent TCR expression may limit efficacy and necessitate repeated infusions. 
 
The non-viral Sleeping Beauty retrotransposon system has also been used to successfully introduce TCRs and CARs into primary T lymphocytes by electroporation, although the attractive simplicity of this plasmid-based gene transfer system is somewhat offset by the reduced transduction efficiency compared with viral vectors, necessitating longer T-cell expansions prior to patient infusion [63,64].
 
...However, improving the anti-tumor efficacy of TCR-T immunotherapy still has several key challenges, including how to safely increase the avidity of therapeutic TCRs, how to identify shared tumor-specific antigens and TCRs in a given patient population, how to utilize personalized TCRs in cancer patients; and what interactions or signals regulate TCR expression and optimal function. Future studies that decipher these and related questions will not only enable a better fundamental understanding of TCR-T therapy, but will also provide as yet untapped opportunities for improved TCR-T treatment efficacy aimed at increasing the overall survival of cancer patients." 
 
 
 


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