Nano-adjuvants and immune agonists promote antitumor immunity of peptide amphiphiles

Yan, Huan; Lin, Guibin; Liu, Zhanyan; Gu, Fei; Zhang, Yuan

doi:10.1016/j.actbio.2023.02.034

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…Various clusters of differentiation (CD) molecules have become attractive targets for NPs targeting LNs, including CD11, CD40, and CD205. [87,88] Most NP targeting strategies for CD molecules involve the use of monoclonal antibodies. [172] NPs, such as liposomes, polymeric NPs, or metallic NPs, can be functionalized with monoclonal antibodies that are specific to CD molecules of interest.…”

Section: Targeting CD Moleculesmentioning

confidence: 99%

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Li,

Zhong,

Cao

et al. 2024

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Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN‐targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future‐oriented discussion, offering critical insights into the field.

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Section: Targeting CD Moleculesmentioning

confidence: 99%

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Li,

Zhong,

Cao

et al. 2024

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“…[34][35][36] Nanovaccines integrating agonistic anti-CD40 antibody as an adjuvant is supposed to be a rational vaccine formulation to elicit more robust and specific antitumor responses. [37] However, preclinical and clinical studies have shown limited therapeutic efficacy due to their complex structures and low in vivo stability. [38,39] Recently, genetically engineered cellular nanovesicles expressing specific proteins have shown the potential to engage the receptors on the immune cell and further promote the downstream signaling, which inspired us to develop nanovaccines based on genetically engineered cellular nanovesicles expressing co-stimulatory molecules CD40L.…”

Section: Introductionmentioning

confidence: 99%

Genetically Engineered Cytomembrane Nanovaccines for Cancer Immunotherapy

Pan,

Wu,

Liu

et al. 2024

Adv Healthcare Materials

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Cancer nanovaccines have attracted widespread attention by inducing potent cytotoxic T cell responses to improve immune checkpoint blockade (ICB) therapy, while the lack of co‐stimulatory molecules limits their clinical applications. Here, we report a genetically engineered cancer cytomembrane nanovaccine that simultaneously overexpresses co‐stimulatory molecule CD40L and immune checkpoint inhibitor PD1 to elicit robust antitumor immunity for cancer immunotherapy. The CD40L and tumor antigens inherited from cancer cytomembranes effectively stimulated dendritic cell (DC)‐mediated immune activation of cytotoxic T cells, while the PD1 on cancer cytomembranes significantly blocked PD1/PD‐L1 signaling pathway, synergistically stimulating antitumor immune responses. Benefited from the targeting ability of cancer cytomembranes, this nanovaccines formula showed an enhanced lymph nodes trafficking and retention. Compared with original cancer cytomembranes, this genetically engineered nanovaccine induced 2‐fold DC maturation and showed satisfactory precaution efficacy in a breast tumor mouse model. This genetically engineered cytomembrane nanovaccine offers a simple, safe, and robust strategy by incorporation of cytomembrane components and co‐stimulatory molecules for enhanced cancer immunotherapy.This article is protected by copyright. All rights reserved

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“…Thus, the secretion of IFN-γ from T cells and nature killer (NK) cells is stimulated, followed by activating and proliferating cytotoxic T lymphocytes (CTLs). 12 Additionally, DOX expresses costimulatory mole-cules and major histocompatibility complex (MHC) and migrates to lymph nodes to activate T cells. Then, antigenspecific T-cell response is triggered, enhancing the activation and running of CIC.…”

Section: Introductionmentioning

confidence: 99%

“…Doxorubicin (DOX) has been proven to trigger tumor ICD. − Tumor cells undergoing ICD can enable TAAs release (CIC step 1), promote the recruitment and maturation of DCs, and then uptake TAAs (CIC step 2). Thus, the secretion of IFN-γ from T cells and nature killer (NK) cells is stimulated, followed by activating and proliferating cytotoxic T lymphocytes (CTLs) . Additionally, DOX expresses costimulatory molecules and major histocompatibility complex (MHC) and migrates to lymph nodes to activate T cells.…”

Section: Introductionmentioning

confidence: 99%

Tumor Microenvironment Sequential Drug/Gene Delivery Nanosystem for Realizing Multistage Boosting of Cancer–Immunity Cycle on Cancer Immunotherapy

Cao,

Li,

Liang

et al. 2023

ACS Appl. Mater. Interfaces

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The antitumor immune response of cancer immunotherapy is a cascade of cancer–immunity cycles (CIC). The immunosuppression of the tumor microenvironment and low immunogenicity of tumor cells, insufficient T lymphocyte activation, trafficking, and infiltration caused the failure to initiate and run the continuous multistage CIC, leading to unsatisfactory cancer immunotherapy outcomes. A doxorubicin/interleukin-12 plasmid DNA/celecoxib (DOX/pIL-12/CXB) combination strategy was designed by targeting the cascade CIC. Then, an intratumoral CXB-detachable nanosystem, or DOX/PAC/pIL-12 micelleplexes, was developed for sequential drug/gene delivery to facilitate the multistage boosting of CIC on synergistic cancer immunotherapy. The DOX/PAC/pIL-12 micelleplexes could program intratumorally sequential release of CXB to remodulate the tumor microenvironment immunosuppression by suppressing the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway. The smaller sizes and surface charge-switched micelleplexes facilitated the codelivery and corelease of DOX and pIL-12 inside 4T1 tumor cells. These micelleplexes exerted a synergistic antitumor immune response using CIC cascade activation and amplification, providing therapeutic antitumor and antimetastasis efficacy. The drug/gene sequential delivery nanosystem provides a complete CIC-boosted combinatory strategy for developing immunotherapy against cancer.

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Nano-adjuvants and immune agonists promote antitumor immunity of peptide amphiphiles

Cited by 7 publications

References 53 publications

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Genetically Engineered Cytomembrane Nanovaccines for Cancer Immunotherapy

Tumor Microenvironment Sequential Drug/Gene Delivery Nanosystem for Realizing Multistage Boosting of Cancer–Immunity Cycle on Cancer Immunotherapy

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