Amplified Cancer Immunotherapy of a Surface-Engineered Antigenic Microparticle Vaccine by Synergistically Modulating Tumor Microenvironment

Zhao, Hongjuan; Zhao, Beibei; Wu, Lixia; Xiao, Hu; Ding, Kaili; Zheng, Cuixia; Song, Qingling; Sun, Lingling; Lei, Wang; Zhang, Zhenzhong

doi:10.1021/acsnano.9b03288

Cited by 89 publications

(58 citation statements)

References 46 publications

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“…Reprograming TAMs toward the anti‐tumor M1‐like phenotype is another promising strategy. [ 47 ] Many cytokines, immunoagonists, and inhibitors against TAMs (such as IL‐12, [ 48 ] CpG oligonucleotides, [ 49–51 ] TLR agonists, [ 47,52–54 ] and miR‐125b [ 55 ] ) can be used to reprogram TAMs. Huang et al.…”

Section: Engineering Macrophages For Cancer Immunotherapymentioning

confidence: 99%

“…[ 59 ] Further, amplified immunotherapy was accomplished by constructing tumor‐derived antigenic microparticles (T‐MPs) loaded with iron oxide nanoparticles and CpG‐containing liposomes, which can convert TAMs to M1 macrophages via nano‐Fe 3 O4 and induce infiltration of cytotoxic T cells. [ 51 ] Similarly, Zhao et al. repolarized TAMs by using ferumoxytol combined or surface‐functionalized with the TLR3 agonist poly(I:C) to promote melanoma regression.…”

Section: Engineering Macrophages For Cancer Immunotherapymentioning

confidence: 99%

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Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

et al. 2020

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was that most nanoparticles do not have a sufficiently long blood half-life and cannot realize deep penetration in tumor tissue. Thus, recent progress in the development of strategies for mimicking or modulating cells offers a highly attractive alternative to drug delivery. [10-17] As natural immune cells and antigenpresenting cells, macrophages [18] have a long blood half-life and can specifically bind to tumor tissue. Therefore, applying macrophages in chemical drug delivery would lead to a significant increase in drug accumulation in tumors. Since macrophages can engulf foreign particles in nature, they can directly phagocytose drugs and then deliver drugs to tumors. [19] Thus, live macrophages may serve as drug carriers. To further increase the tumor-targeting ability of macrophages, they can be engineered with targeting ligands. [20] In addition, learning from red blood cell (RBC) membrane coating technology, [21-23] a macrophage cell membrane coating was developed and it resulted in enhanced tumor uptake of drugs. On the other hand, macrophages play an important role in modulating the tumor immune microenvironment. M1 macrophages inhibit tumor growth, while M2 macrophages promote tumor growth. Inhibition of M2 macrophages and repolarization of M2 macrophages to M1 macrophages are common strategies to treat solid tumors. Furthermore, since these macrophages express SIRPα on their surface, their phagocytic activity against CD47-expressing tumor cells is significantly affected by the CD47-SIRPα pathway. Therefore, blocking the CD47-SIRPα pathway can further enhance the anti-tumor efficacy of macrophages. Herein, to elucidate the importance of macrophages in tumor therapy (Figure 1), we will first discuss the role of macrophages in cancer immunotherapy, including the inhibition, depletion, and repolarization of tumor-associated macrophages (TAMs) and the blocking of the CD47-SIRPα pathway to enhance phagocytosis in tumor therapy. Then, based on the tumor targeting of M1 macrophages, we will discuss the applications of macrophages, macrophage-derived exosomes, and macrophage-coated NPs for drug delivery. We will thus offer a comprehensive understanding of functionalizing macrophages for tumor therapy. Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while antiinflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are ela...

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Section: Engineering Macrophages For Cancer Immunotherapymentioning

confidence: 99%

Section: Engineering Macrophages For Cancer Immunotherapymentioning

confidence: 99%

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

et al. 2020

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“…Nano‐Fe 3 O 4 is encapsulated in T‐MPs to prepare Fe 3 O 4 /T‐MPs, which are tethered with CpG‐loaded liposomes on the surface to generate a vaccine of Fe 3 O 4 /T‐MPs‐CpG/Lipo. This nano‐modified T‐MP vaccine elicits strong antitumor T‐cell immune response by triggering DC antigen cross‐presentation [65]. In addition, studies from the Mooney's group have explored two mechanical approaches (extrusion and sonication, respectively) to produce subcellular vesicles, and they demonstrated that adjuvant (CpG)‐loaded such microvesicles can present tumor antigens to DCs and induce antitumor T‐cell response [66].…”

Section: T‐mps Act As Potential Cancer Vaccinesmentioning

confidence: 99%

Tumor‐derived microparticles in tumor immunology and immunotherapy

Zhang

Tang

et al. 2020

Eur J Immunol

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Microvesicles or microparticles, a type of cytoplasm membrane‐derived extracellular vesicles, can be released by cancer cells or normal cell types. Alteration of F‐actin cytoskeleton by various signals may lead to the cytoplasm membrane encapsulating cellular contents to form microparticles, which contain various messenger molecules, including enzymes, RNAs and even DNA fragments, and are released to extracellular space. The release of microparticles by tumor cells (T‐MPs) is a very common event in tumor microenvironments. As a result, T‐MPs not only influence tumor cell biology but also profoundly forge tumor immunology. Moreover, T‐MPs can act as a natural vehicle that delivers therapeutic drugs to tumor cells and immune cells, thus, remodeling tumor microenvironments and resetting antitumor immune responses, thus, conferring T‐MPs a potential role in tumor immunotherapies and tumor vaccines. In this review, we focus on the double‐edged sword role of T‐MPs in tumor immunology, specifically in TAMs and DCs, and emphasize the application of drug‐packaging T‐MPs in cancer patients. We aim to provide a new angle to understand immuno‐oncology and new strategies for cancer immunotherapy.

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“…Besides, immune checkpoint PD-L1 blockade and Lipo/Fe3O4/T-MPsCpG vaccine synergistically enhanced the anti-tumor immunity of mice, significantly prolonging the survival period of mice to 3 months. [93]…”

Section: Nano Vaccinementioning

confidence: 99%

“…The results indicated that the T‐MPS‐CpG/Lipo/Fe3O4 vaccine could transform cold cancer into hot cancer by adjusting the time and space of TME, thereby maximizing the induction of anti‐tumor immunity. Besides, immune checkpoint PD‐L1 blockade and Lipo/Fe3O4/T‐MPsCpG vaccine synergistically enhanced the anti‐tumor immunity of mice, significantly prolonging the survival period of mice to 3 months [93] …”

Section: Combination Of Nanotechnology‐based Immune Checkpoint Blockimentioning

confidence: 99%

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

Sun

et al. 2020

ChemistrySelect

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Tumor immunotherapy has received worldwide attention in cancer treatment owing to its apparent advantages, such as strong specificity and long curative effect. Among them, significant progress has been made on the immune checkpoint therapy in recent years. FDA approved PD‐L1/PD‐1 and CTLA‐4 immune checkpoint inhibitors have been broadly used in a variety of malignant tumors. However, because of the low response rate of immune checkpoint drugs, its clinical application has been greatly hindered. With the prominence of nanotechnology in bio‐medicine, the application of nanotechnology in immune checkpoints has also gained more and more attention. The combination of radiotherapy, chemotherapy, phototherapy, magnetic therapy and other methods in nanotechnology makes an excellent promoting effect in the treatment of immune checkpoint drugs. This article reviews the recent breakthroughs of nanotechnology in immune checkpoint blocking therapy, mainly focusing on the significant advantages of the combination of nanotechnology‐based immune checkpoint blocking therapy with other treatment methods. In addition, we also discussed the challenges in this area and pointed out some potential directions for future development.

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Amplified Cancer Immunotherapy of a Surface-Engineered Antigenic Microparticle Vaccine by Synergistically Modulating Tumor Microenvironment

Cited by 89 publications

References 46 publications

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

Tumor‐derived microparticles in tumor immunology and immunotherapy

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

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