
Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 882 - 882
Published: April 5, 2025
Objectives: Pancreatic cancer remains a therapeutic challenge due to its immunosuppressive microenvironment and treatment resistance. This study aimed develop novel recombinant oncolytic vaccinia virus (VVL-GL7) co-expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) interleukin-7 (IL-7), designed enhance anti-tumor immunity synergize with immune checkpoint inhibitors. Methods: VVL-GL7 was constructed through CRISPR/Cas9-mediated knockout of TK A49 genes, combined the simultaneous insertion dual cytokine-encoding cassettes. Anti-tumor efficacy evaluated in vitro vivo using C57BL/6 mouse Syrian hamster pancreatic models. Comprehensive profiling CD8+ T-cell macrophage infiltration dynamics while simultaneously assessing memory differentiation patterns flow cytometry. Preclinical combination studies PD-1 inhibitor were systematically syngeneic model. Results: exhibited potent activity, inducing significant tumor regression both preclinical therapy significantly augmented within microenvironment, concomitantly driving differentiation. The synergistic effects blockade further improved outcomes, resulting higher remission rates compared monotherapy achieving complete Conclusions: reprograms synergizes anti-PD-1 antibodies overcome resistance cancer.
Language: Английский