Bifunctional Fusion Membrane‐Based Hydrogel Enhances Antitumor Potency of Autologous Cancer Vaccines by Activating Dendritic Cells

Abstract

Autologous tumor cell vaccine is an individualized tumor treatment strategy to elicit tumor-specific immune responses. However, it is difficult to exert efficacy in "cold" tumors, which lack tumor-infiltrating T cells and are not sensitive to immunotherapy. Here, a dendritic cells (DCs) activation hydrogel is constructed based on bifunctional fusion membrane nanoparticles (FM-NPs) composed of autologous tumor cell membranes and Mycobacterium phlei membrane extracts. The FM-NPs not only provide tumor antigens but also can activate DCs. Afterward, the FM-NPs are loaded in an injectable alginate hydrogel together with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF releases rapidly and recruits DCs to hydrogel, while FM-NPs retain in hydrogel to continuously interconnected with DCs, enriching mature DCs loaded with tumor antigens. In the 4T1 mouse breast tumor model, this hydrogel promotes the maturation of DCs in tumordraining lymph nodes and induces sufficient effector memory T cells that migrate to the tumor microenvironment. This successfully converts the "cold" tumors to "hot", thus exerting a significant antitumor effect synergized with the PD-1 antibody. It is also verified the inhibitory effect of FM-NPs using human gastric cancer organoids. Altogether, these findings demonstrate the application potential for the bifunctional fusion membrane-based hydrogel as an autologous tumor vaccine by activating DCs.

Smart Nanoparticle‐Based Platforms for Regulating Tumor Microenvironment and Cancer Immunotherapy

“…Furthermore, the hydrogel could enhance the maturation of DCs in tumor-draining lymph nodes and induce the differentiation of effector memory T cells, migrating to the TME and converting the cold tumor to the hot tumor. [65] Zhang et al prepared tumor-permeated adenosine triphosphate (ATP)-based NPs as the ATP is necessary for triggering the eat-me signal in immunogenic cell death (ICD). Before arriving at the tumor, the NPs can protect ATP from degradation.…”

“…Furthermore, the hydrogel could enhance the maturation of DCs in tumor‐draining lymph nodes and induce the differentiation of effector memory T cells, migrating to the TME and converting the cold tumor to the hot tumor. [ 65 ]…”

“…Schematic depiction of a) preparing the FM-NPs, b) preparing the GM-SCF and FM-NPs contained alginate-cation hydrogels,and c) the hydrogel inducing the DCs maturation and activating the effector T cells to inhibit the tumor. Reproduced with permission [65]. Copyright 2022, Wiley-VCH GmbH.…”

“…CellBiomarkers Functions in the cancer immunotherapy NPs applied for regulating cells. Ref.DCs CD40, CD86, and CD103Mediating anti-tumor immune response, inducing the differentiation of effector memory T cells,[65][66][67] …”

Trident Molecule with Nanobrush–Nanoparticle–Nanofiber Transition Property Spatially Suppresses Tumor Metastasis

“…Quantitatively, on day 14 post injection, while the average tumor volume of the Nap – CPT – HCQ – Yp -treated group was 28.6% of that of the PBS group, that of the “ Nap – CPT – HCQ – Yp + aPD-1”-treated group dropped to 10.0% of PBS groups. Furthermore, it has been reported that aPD-1 treatment alone showed minor effects on tumor growth. − These results suggested that the following aPD-1 treatment additionally enhanced the primary tumor-inhibitory effect of Nap – CPT – HCQ – Yp (Figure c). H&E staining results in Figure d exhibited that, among the five groups, the most significant tumor cell apoptosis/death of the primary tumors and the least lung metastasis nodules were observed in the “ Nap – CPT – HCQ – Yp + aPD-1” group.…”