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Preclinical data from another group: 'Hepatocellular carcinoma (HCC)

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jondoeuk   Tuesday, 05/25/21 08:04:46 PM
Re: jondoeuk post# 164
Post # of 167 
Preclinical data from another group: ''Hepatocellular carcinoma (HCC) is responsible for most of primary liver cancer cases and is the sixth most common cancer in the world with a general 5 year survival rate of 18% due to lack of effective therapy. Adoptive T-cell therapy (ACT) with T-cell receptor–engineered T-cell (TCR-T) against HCC-associated antigen a-fetoprotein (AFP), can redirect human T cells to recognize and kill HCC tumor cells.

However, the clinical efficacy of TCR-T therapy is dependent on the proper expansion, in vivo persistence of T cells that is markedly reduced due to exhaustion-associated dysfunction, and activation induced cell death. To improve persistence of TCR-T cells without modifying TCR affinity, we engineered TCR-T cells to overexpress c-Jun, an AP-1 transcription factor associated with T cell development and activation. In this study, we showed that TCR-T cells overexpressing c-Jun have enhanced expansion capacity in culture, improved cytokine production against HepG2 tumor cells without altering their cytotoxic potential.

Interestingly TCR-T cells overexpressing c-Jun showed resistance to activation induced cell death with decreased expression of inhibitory receptors after stimulation with HepG2 tumor cells. Thus, c-Jun overexpression could be a potential therapeutic agent to enhance the anti-tumor efficacy of TCR-T cells against HCC.''

https://virtual.aai.org/aai/2021/virtual-immunology-2021/317351/mohamed.hussein.the.role.of.c-jun.in.enhancing.tcr-t.function.in.treatment.of.html

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