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

Research output: Contribution to journalConference articleContributedpeer-review

Contributors

  • Ana I Matos - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Carina Peres - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Barbara Carreira - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Liane I F Moura - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Rita C Acúrcio - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Theresa Vogel - , Dresden University of Technology (Author)
  • Erik Wegener - , Chair of Macromolecular Chemistry (Author)
  • Filipa Ribeiro - , Lisbon Academic Medical Center (Author)
  • Marta B Afonso - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Fábio M F Santos - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Águeda Martínez-Barriocanal - , Vall d'Hebron Research Institute (VHIR) (Author)
  • Diego Arango - , Vall d'Hebron Research Institute (VHIR) (Author)
  • Ana S Viana - , Institute of Molecular Biotechnology (IMBA) (Author)
  • Pedro M P Góis - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Liana C Silva - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Cecília M P Rodrigues - , Research Institute for Medicines (iMed.ULisboa) (Author)
  • Luis Graca - , Lisbon Academic Medical Center (Author)
  • Rainer Jordan - , Chair of Macromolecular Chemistry (Author)
  • Ronit Satchi-Fainaro - , Tel Aviv University (Author)
  • Helena F Florindo - , Research Institute for Medicines (iMed.ULisboa) (Author)

Abstract

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

Details

Original languageEnglish
Article number2300299
Pages (from-to)e2300299
Number of pages22
JournalAdvanced Science
Volume10
Issue number25
Early online date11 Jul 2023
Publication statusPublished - 5 Sept 2023
Peer-reviewedYes

External IDs

Scopus 85164453502
Mendeley 3df83403-9626-3117-9130-c2c07cff33be
WOS 001026332700001

Keywords

Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Sustainable Development Goals

Keywords

  • anti-PD-1, nanovaccines, poly(2-oxazoline)s, tumor immune microenvironment, tumor-associated macrophages, Poly(2-oxazoline)s, Tumor immune microenvironment, Nanovaccines, Tumor-associated macrophages, Melanoma, Tumor Microenvironment, CD8-Positive T-Lymphocytes, Animals, Immunotherapy, Cell Line, Tumor, Tumor-Associated Macrophages, Mice