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

被引：12

作者：

Matos, Ana I. I. ^{[1
,2
]}

Peres, Carina ^{[1
,2
]}

Carreira, Barbara ^{[1
]}

Moura, Liane I. F. ^{[1
]}

Acurcio, Rita C. C. ^{[1
]}

Vogel, Theresa ^{[3
]}

Wegener, Erik ^{[3
]}

Ribeiro, Filipa ^{[2
]}

Afonso, Marta B. B. ^{[1
]}

Santos, Fabio M. F. ^{[1
]}

Martinez-Barriocanal, Agueda ^{[4
,5
]}

Arango, Diego ^{[4
,5
]}

Viana, Ana S. S. ^{[6
]}

Gois, Pedro M. P. ^{[1
]}

Silva, Liana C. C. ^{[1
]}

Rodrigues, Cecilia M. P. ^{[1
]}

Graca, Luis ^{[2
]}

Jordan, Rainer ^{[3
]}

Satchi-Fainaro, Ronit ^{[7
]}

Florindo, Helena F. F. ^{[1
]}

机构：

[1] Univ Lisbon, Res Inst Med iMed ULisboa, Fac Pharm, Dept Pharm Pharmacol & Hlth Technol,Grouf BioNanoS, P-1649003 Lisbon, Portugal

[2] Univ Lisbon, Fac Med, Lisbon Acad Med Ctr, Inst Med Mol Joao Lobo Antunes, P-1649028 Lisbon, Portugal

[3] Tech Univ Dresden, Fac Chem & Food Chem, Sch Sci, Dept Chem, D-01062 Dresden, Germany

[4] Univ Autonoma Barcelona UAB, Vall dHebron Res Inst VHIR, Grp Biomed Res Digest Tract Tumors, CIBBIM Nanomed, Barcelona 08035, Spain

[5] Lleida Biomed Res Inst IRBLleida, Grp Mol Oncol, Lleida 25198, Spain

[6] Univ Lisbon, Inst Mol Sci, Fac Sci, Ctr Quim Estrutural,Dept Quim & Bioquim, P-1749016 Lisbon, Portugal

[7] Tel Aviv Univ, Fac Med, Sagol Sch Neurosci, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel

来源：

ADVANCED SCIENCE | 2023年 / 10卷 / 25期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

anti-PD-1; nanovaccines; poly(2-oxazoline)s; tumor immune microenvironment; tumor-associated macrophages; DENDRITIC CELLS; COLORECTAL-CANCER; DELIVERY-SYSTEMS; T-CELLS; ANTITUMOR IMMUNITY; PATIENTS PTS; LYMPH-NODES; NANOPARTICLES; ACTIVATION; RESPONSES;

D O I：

10.1002/advs.202300299

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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)-& beta; 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.

引用

页数：22

共 94 条

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