AAV-IL-27

AAV-IL-27 is a gene therapy using recombinant adeno-associated virus (rAAV) to deliver and express the cytokine interleukin-27 (IL-27) in vivo, primarily for cancer immunotherapy. AAV-IL-27 acts by inhibiting tumor growth and enhancing anti-tumor immunity[1][2][3][8]. Its key mechanisms include rapid depletion of regulatory T cells (Tregs) via IL-27 receptor and Stat1 signaling, downregulation of CD25 in Tregs, and inhibition of IL-2 production by T cells, thereby amplifying T cell responses against tumors[1][2][8]. AAV-IL-27 also induces PD-L1 expression in T cells, which increases sensitivity to anti–PD-1 therapies[1][3][8]. This therapy has shown synergistic effects with GM-CSF vaccines and PD-1 antibodies, greatly improving tumor rejection and long-term survival in preclinical studies[1][3][8]. It does not cause significant autoimmunity or toxicity, partly due to induction of IL-10[1][2]. AAV-IL-27 has also demonstrated efficacy in autoimmune disease models by inhibiting Th17 cell responses and GM-CSF-producing T cells[5].