STAT5 Activation Enhances Adoptive Therapy Combined with Peptide Vaccination by Preventing PD-1 Inhibition

Adoptive cell therapy (ACT) using retrovirally transduced CD8 T cells and subsequently vaccinated with TriVax. We T cells represents a promising strategy for enhancing antitumor demonstrate that TriVax selectively enhanced the expansion of responses. When used with TriVax, a peptide vaccination strat- ACT cell populations bearing gp100-specific TCRs. T cells engiegy, this approach synergistically expands antigen-specific cell neered to express CA-STAT5 showed not only increased ex-populations. STAT5 plays a vital role as a transcription factor in pansion and polyfunctionality but also reduced PD-1 expression, regulating T-cell proliferation and their differentiation into ef- leading to decreased cellular exhaustion. In a B16F10 melanoma fector and memory T cells. We aimed to explore the combination mouse model, our approach yielded a potent antitumor effect, therapy using CD8 T cells engineered to express constitutively with CA-STAT5 further amplifying this response. We found that active STAT5 (CA-STAT5) with vaccines. CD8 T cells were CA-STAT5 improved antitumor activities, in part, by attenuating transduced with a retrovirus (RV) encoding the mouse the PD-1/PD-L1 inhibitory pathway. These findings indicate that gp100 T-cell receptor (TCR). In certain treatment groups, cells TCR-transduced CD8 T cells can undergo antigen-dependent were also co-transduced with RV encoding CA-STAT5. We expansion when exposed to TriVax. Additionally, the expression assessed transduction efficiency and functional activity through of CA-STAT5 enhances T-cell proliferation and persistence, flow cytometry and various functional assays. B16F10 tumor- partly by promoting resistance to PD-1/PD-L1–mediated inhibearing mice were treated with ACT using RV-transduced bition in antitumor T cells.