基于杂合M13噬菌体的个性化癌症疫苗平台用于肿瘤免疫治疗研究

Abstract

Although cancer vaccines exhibit great advances in the field of immunotherapy, developing an efficient vaccine platform for personalized tumor immunotherapy is still a major challenge. Here we demonstrate that a bioactive vaccine platform ( [email protected] ) fabricated with hybrid M13 phage and personal tumor antigens can facilitate delivery of antigens into lymph nodes and activate antigen-presenting cells (APCs) through the Toll-like receptor 9 (TLR9) signaling pathway , which boosts both innate and adaptive immune response. As an adjuvant platform, hybrid M13 phages can deliver various tumor-specific antigens through simple adsorption to support the current development of personalized vaccines for cancers. Notably, the [email protected] vaccine not only prevented the tumors, but also delayed the tumor growth in established (subcutaneous and orthotopic) and metastatic tumor-bearing models while synergy with immune checkpoint blockade (ICB) therapy. Moreover, [email protected] triggered a robust neoantigen-based specific immune response in tumor-specific mutation models. In a clinically relevant surgery model, using autologous cell membrane from primary tumors-based [email protected] cooperation with ICB dramatically inhibited the post-operation recurrence, and elicited a long-term immune memory effect simultaneously. These findings imply that the M13 phage represents a powerful tool to develop a bio-activated hybrid platform for personalized therapy.