TY - JOUR
T1 - Polyoxazoline-Based Nanovaccine Synergizes with Tumor-Associated Macrophage Targeting and Anti-PD-1 Immunotherapy against Solid Tumors
AU - Matos, Ana I.
AU - Peres, Carina
AU - Carreira, Barbara
AU - Moura, Liane I.F.
AU - Acúrcio, Rita C.
AU - Vogel, Theresa
AU - Wegener, Erik
AU - Ribeiro, Filipa
AU - Afonso, Marta B.
AU - Santos, Fábio M.F.
AU - Martínez-Barriocanal, Águeda
AU - Arango, Diego
AU - Viana, Ana S.
AU - Góis, Pedro M.P.
AU - Silva, Liana C.
AU - Rodrigues, Cecília M.P.
AU - Graca, Luis
AU - Jordan, Rainer
AU - Satchi-Fainaro, Ronit
AU - Florindo, Helena F.
N1 - Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2023/9/5
Y1 - 2023/9/5
N2 - 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.
AB - 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.
KW - anti-PD-1
KW - nanovaccines
KW - poly(2-oxazoline)s
KW - tumor immune microenvironment
KW - tumor-associated macrophages
UR - http://www.scopus.com/inward/record.url?scp=85164453502&partnerID=8YFLogxK
U2 - 10.1002/advs.202300299
DO - 10.1002/advs.202300299
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C2 - 37434063
AN - SCOPUS:85164453502
SN - 2198-3844
VL - 10
JO - Advanced Science
JF - Advanced Science
IS - 25
M1 - 2300299
ER -