Macrophage-derived implantable vaccine prevents postsurgical tumor recurrence

Wang, Dongqing; Xue, Mingming; Chen, Heying; Liu, Jiahe; Li, Qianyin; Xie, Yajun; Hu, Yi; Ni, Yilu; Zhou, Qin

doi:10.1016/j.biomaterials.2021.121161

Cited by 20 publications

(12 citation statements)

References 47 publications

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“…Wang et al isolated membranes from fused M1 macrophage-inactive 4T1 cancer cells to load cytosinephosphate-guanosine oligodeoxynucleotides (CpG ODNs) to obtain the nanovaccines FM+, and then embedded FM+ into a hydrogel for postsurgical tumor recurrence prevention. [139] Cell fusion technology endows the fused macrophage-cancer cells with costimulatory molecules and complex tumor antigenic profile from both parental cells. In this way, the obtained fused cell membranes had the effective combination of tumor antigens and macrophage membranes.…”

Section: Nps Coated With Hybrid Membranesmentioning

confidence: 99%

Immunocyte‐Derived Nanodrugs for Cancer Therapy

Zhu

Wang

Jia

et al. 2022

Adv Funct Materials

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Recent years have witnessed the rapid development of the biomimetic nanotechnology regarding the use of certain components (such as cell membranes, extracellular vesicles, proteins, etc.) derived from different cells to fabricate nanoparticles (NPs) for cancer treatment. These biomimetic NPs usually inherit certain abilities from their parental cells, such as long blood circulation, capacity to escape from mononuclear phagocytic system, active tumor‐targeting, and controlled drug release. Immunocytes play vital roles in different tumor progression stages, and can quickly and accurately react to tumor progression via specific targeting and immune surveillance. Therefore, increasing studies focus on constructing biomimetic NPs with components isolated from immunocytes. This review introduces four main types of immunocyte‐derived nanodrugs—membrane‐coated NPs, exosomes or extracellular vesicles, functional protein‐incorporated NPs, and exosome mimetics—and summarizes the recent advances of these nanodrugs for cancer therapy. Some current challenges and future research directions of immunocyte‐derived nanodrugs are also proposed. It is hoped that this review may help researchers in the related field to design new immunocyte‐derived nanomedicines and promote their preclinical and clinical applications in the near future.

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Section: Nps Coated With Hybrid Membranesmentioning

confidence: 99%

Immunocyte‐Derived Nanodrugs for Cancer Therapy

Zhu

Wang

Jia

et al. 2022

Adv Funct Materials

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“…M1 macrophages display important antitumor activities and are involved in the immune system’s response to cancer, whereas M2 macrophages (also known as tumor-associated macrophages or M2-TAMs) promote cancer progression and contribute to multidrug resistance in cancer therapy [ 5 , 6 ]. Therefore, multiple antitumoral approaches are being explored to induce the shift of M2-TAMs to proinflammatory M1 macrophages [ 7 , 8 , 9 ]. Among the new immunotherapeutic treatments, approaches based on extracellular vesicles (EVs) are receiving attention for their antitumor potential and the bioengineering possibilities that they can offer [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a β-Blocker Potentiate Doxorubicin’s Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer

et al. 2022

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One of the main reasons for cancer’s low clinical response to chemotherapeutics is the highly immunosuppressive tumor microenvironment (TME). Tumor-ass ociated M2 macrophages (M2-TAMs) orchestrate the immunosuppression, which favors tumor progression. Extracellular vesicles (EVs) have shown great potential for targeted therapies as, depending on their biological origin, they can present different therapeutic properties, such as enhanced accumulation in the target tissue or modulation of the immune system. In the current study, EVs were isolated from M1-macrophages (M1-EVs) pre-treated with hyaluronic acid (HA) and the β-blocker carvedilol (CV). The resulting modulated-M1 EVs (MM1-EVs) were further loaded with doxorubicin (MM1-DOX) to assess their effect in a mouse model of metastatic tumor growth. The cell death and cell migration profile were evaluated in vitro in 4T1 cells. The polarization of the RAW 264.7 murine macrophage cell line was also analyzed to evaluate the effects on the TME. Tumors were investigated by qRT-PCR and immunohistochemistry. MM1-DOX reduced the primary tumor size and metastases. NF-κB was the major gene downregulated by MM1-DOX. Furthermore, MM1-DOX reduced the expression of M2-TAM (CD-163) in tumors, which resulted in increased apoptosis (FADD) as well as decreased expression of MMP-2 and TGF-β. These results suggest a direct effect in tumors and an upregulation in the TME immunomodulation, which corroborate with our in vitro data that showed increased apoptosis, modulation of macrophage polarization, and reduced cell migration after treatment with M1-EVs combined with HA and CV. Our results indicate that the M1-EVs enhanced the antitumor effects of DOX, especially if combined with HA and CV in an animal model of metastatic cancer.

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“…However, most of the cytomembrane strategies are involved with chemical materials or synthetic drugs, the biosecurity problems like chemical toxicity or long‐term retention are of great concern in clinical trial 28,29 . Previously, we have manufactured a tumor vaccine based on fused cytomembrane (derived from macrophages) to induce robust immune responses and prevent tumor recurrence 30 . Thus, we intend to take further advantages of the bio‐affinitive and co‐stimulatory merits in cytomembrane, proposing a chemical materials‐, exogenous antigens‐ and adoptive cells‐free modality to provide a biosafe solution for skin wound repair.…”

Section: Introductionmentioning

confidence: 99%

“… 28 , 29 Previously, we have manufactured a tumor vaccine based on fused cytomembrane (derived from macrophages) to induce robust immune responses and prevent tumor recurrence. 30 Thus, we intend to take further advantages of the bio‐affinitive and co‐stimulatory merits in cytomembrane, proposing a chemical materials‐, exogenous antigens‐ and adoptive cells‐free modality to provide a biosafe solution for skin wound repair.…”

Section: Introductionmentioning

confidence: 99%

Biofabricated macrophage and fibroblast membranes synergistically promote skin wound healing

Wang

Chen

et al. 2022

Bioengineering & Transla Med

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Effective skin wound healing is a complex process involving anti-inflammation, fibrosis, matrix reconstruction, and angiogenesis. This work aimed to integrate the macrophage-mediated anti-inflammation and fibroblast-assisted matrix reconstruction for enhanced skin wound healing. Herein, we utilized the cytomembranes derived from repolarized M2 macrophages and fibroblasts to prepare the natural biologics. Results showed that the inflammatory M1 macrophages were repolarized to M2 phenotype by the M2 macrophage cytomembranes. As a consequence, the cytomembranes of M2 macrophage could facilitate the wound closure in mice. Furthermore, the addition of fibroblast membranes to the macrophage cytomembranes contributed to a better matrix reconstruction, neovascularization and angiogenesis.Next, we used a transforming growth factor-β (TGF-β) inhibitor to attenuate cutaneous scar formation. Therefore, our modality could promote skin wound healing and effectively suppress scar formation in the preclinical murine skin wounds. The cytomembrane biologics might provide a biocompatible and versatile tool for wound healing.

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Macrophage-derived implantable vaccine prevents postsurgical tumor recurrence

Cited by 20 publications

References 47 publications

Immunocyte‐Derived Nanodrugs for Cancer Therapy

Immunocyte‐Derived Nanodrugs for Cancer Therapy

Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a β-Blocker Potentiate Doxorubicin’s Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer

Biofabricated macrophage and fibroblast membranes synergistically promote skin wound healing

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