jondoeuk
4 years ago
New NY-ESO-1 TCR-T data https://jitc.bmj.com/content/7/1/276
From it: ''These data provide an initial rationale as to how tumors with histologies resistant to checkpoint blockade can be successfully targeted with adoptive T-cell therapy. Furthermore, these data are the first to demonstrate successful infiltration of solid tumors by SPEAR T cells, which are able to kill tumor cells. Our data also suggest that antigen loss or alterations in the expression of antigen processing proteins are not primary mechanisms of resistance. Moreover, the therapeutic efficacy may be enhanced through use of a high dose fludarabine-containing preparative lymphodepletion regimen, by promoting greater engraftment at the tumor site, and through modulation of TAM.''
jondoeuk
4 years ago
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 receptorโengineered 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