Polyoxazoline‐Based Nanovaccine Synergizes with Tumor‐Associated Macrophage Targeting and Anti‐PD‐1 Immunotherapy against Solid Tumors

• DOI: 10.1002/advs.202300299
• Publication Date: 2023-07-12T03:09:41Z
• Authors: Ana I. Matos; Carina Peres; Barbara Carreira; Liane I. F. Moura; Rita C. Acúrcio; Theresa Vogel; Erik Wegener; Filipa Ribeiro; Marta B. Afonso; Fábio M. F. Santos; Águeda Martínez‐B...; Diego Arango; Ana S. Viana; Pedro M. P. Góis; Liana C. Silva; Cecília M. P. Rod...; Luis Graca; Rainer Jordan; Ronit Satchi‐Fainaro; Helena F. Florindo
• Keywords: Cancer Immunotherapy

Abstract Immune checkpoint blockade reaches remarkable clinical responses. However, even in the most favorable cases, half of these patients do not benefit from therapies long term. It is hypothesized that activation host immunity by co‐delivering peptide antigens, adjuvants, and regulators transforming growth factor (TGF)‐β expression using a polyoxazoline (POx)‐poly(lactic‐ co ‐glycolic) acid (PLGA) nanovaccine, while modulating tumor‐associated macrophages (TAM) function within tumor microenvironment (TME) blocking anti‐programmed cell death protein 1 (PD‐1) can constitute an alternative approach for cancer immunotherapy. POx‐Mannose (Man) nanovaccines generate antigen‐specific T‐cell responses control to higher extent than poly(ethylene glycol) (PEG)‐Man nanovaccines. This anti‐tumor effect induced POx‐Man mediated CD8 + ‐T cell‐dependent mechanism, contrast PEG‐Man nanovaccine combines with pexidartinib, modulator TAM function, restricts MC38 growth, synergizes PD‐1 blockade, controlling CT26 survival. data further validated highly aggressive poorly immunogenic B16F10 melanoma mouse model. Therefore, synergistic combination inhibition both TAM‐ PD‐1‐inducing immunosuppression, holds great potential improving immunotherapy outcomes solid patients.