Interleukin-12 enhances the function and anti-tumor activity in murine and human CD8(+) T cells.

摘要: Mouse CD8+ T cells conditioned with interleukin (IL)-12 ex vivo mediate the potent regression of established melanoma when transferred into lymphodepleted mice. However, quantitative and qualitative changes induced by IL-12 in responding mouse have not been well defined. Moreover, mechanisms which IL-12-conditioning impacts human cells, how such might be expanded prior to infusion patients is known. We found that led a tenfold–100-fold increase persistence anti-tumor efficacy upon adoptive transfer The enhancing effect was associated maintenance functional avidity. Importantly, context ongoing ACT clinical trials, genetically modified tyrosinase-specific cell receptor (TCR) exhibited significantly enhanced activity as indicated heightened granzyme B expression elevated peptide-specific CD107a degranulation. This sustainable despite 20 days vitro cellular expansion required expand over 1,000-fold allowing adequate numbers for administration cancer patients. Overall, these findings support feasibility TCR-modified therapy.