Mannose and Hyaluronic Acid Dual-Modified Iron Oxide Enhances Neoantigen-Based Peptide Vaccine Therapy by Polarizing Tumor-Associated Macrophages

Abstract

Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein, we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1 phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability, while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo. Combined with antigenic peptides, this nanovaccine could significantly increase the infiltration of CD8+ T cells into tumor tissue and strongly activate dendritic cells in sentinel lymph nodes. Finally, we used the dual-modified nanoparticles to first convert the tumor microenvironment and then the nanovaccine administration in a TC1 tumor model to further enhance efficacy. This strategy inhibited tumor growth and achieved a 40% cure rate in mice (two of five). In summary, this study provides a potent and rationally designed nanoadjuvant to enhance antitumor efficiency and facilitate delivery of neoantigen vaccines by repolarizing TAMs and harmonizing immune cells.

Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering

“…It was also shown that OVA conjugated to the polymer enhanced the humoral and cellular immunity compared with the OVA conjugated to polymers lacking either mannose or the adjuvant [ 121 ]. Many mannose-conjugated nanoformulations are currently available, for delivering therapeutic agents [ [122] , [123] , [124] ], detecting sentinel LNs [ [125] , [126] , [127] ], etc .…”

Emerging advances in nanobiomaterials-assisted chimeric antigen receptor (CAR)-macrophages for tumor immunotherapy

“…Macrophages are a diverse and intricate group of cells infiltration the tumor microenvironment ( Wagner et al, 2019 ; Christofides et al, 2022 ). Based on the classical paradigms of M1 and M2 phenotypes with pro-inflammatory and anti-inflammatory properties, the mainstream anti-tumor therapy for TAM mainly focuses on the strategies for depletion ( Mazzieri et al, 2011 ; Germano et al, 2013 ), remodeling TAM including polarization or reactivation ( Hoves et al, 2018 ; Eisinger et al, 2020 ; Yang et al, 2020 ; Anfray et al, 2021 ; Sun et al, 2021 ; Nie et al, 2022 ), and inhibition of monocyte or macrophage recruitment into tumors ( Qian et al, 2011 ; Mantovani et al, 2017 ; Cassetta and Pollard, 2018 ). Recently, a large number of clinically developed drugs mainly focus on the targets CSF-1R, CD47, CD40, and chemokines ( Beatty et al, 2011 ; Yanagita et al, 2017 ; Sikic et al, 2019 ; Sylvestre et al, 2020 ).…”

Tumor-associated macrophages in nanomaterial-based anti-tumor therapy: as target spots or delivery platforms

“…Meanwhile, in a recent study, Nie et al were able to used mannose to confer TAM targeting ability, while HA and iron oxide were used to repolarize M2-like TAM. The NPs developed by Nie et al significantly improved the targeting success rate and the cure rate in mice ( Nie et al, 2022 ).…”