Two‐Pronged Intracellular Co‐Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy

Meng, Junwei; Zhang, Peisen; Chen, Qizhe; Wang, Zihua; Gu, Yuan; Ma, Jie; Li, Wang; Yang, Chen; Qiao, Yuanyuan; Hou, Yi; Jing, Lihong; Wang, Yong; Gu, Zi; Zhu, Lichong; Xu, HengYu; Lu, Xueguang; Gao, Mingyuan

doi:10.1002/adma.202202168

Cited by 59 publications

(40 citation statements)

References 60 publications

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“…Bone marrow-derived dendritic cells (BMDCs) were induced and then incubated with np CpG, free CpG, and empty nanoparticles (eNPs), respectively. The production of co-stimulatory molecules and cytokines is an important marker for evaluating the maturation efficacy of DCs. , The results showed that np CpG, in contrast to any other controls, significantly upregulated the expression of CD40, CD80, and CD86 (Figure c and Figure S1 of the Supporting Information). Similarly, the secretion of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and Th1-polarizing cytokine IL-12 was more notably promoted following stimulation with np CpG than with other groups (Figure d).…”

Section: Resultsmentioning

confidence: 97%

Universal and Translational Nanoparticulate CpG Adjuvant

Qiao

Liu

et al. 2022

ACS Appl. Mater. Interfaces

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CpG, an agonist of toll-like receptor 9 (TLR9), has become a novel adjuvant that substantially potentiates cellular immunity. However, this agonist may increase systemic toxicity by diffusing into blood after administration and is difficult to be internalized by immune cells to reach TLR9 located in endosomes as a result of the characteristics of negative charge of CpG. Here, we applied a scalable and controllable flash nanocomplexation technology to prepare nanoparticulate CpG adjuvant (npCpG), CpG encapsulated in a physical cross-linking network of protamine and TPP. The nanoadjuvant could redirect CpG into draining lymph nodes to reduce systemic diffusion to improve safety. Further, a combination of npCpG and influenza H1N1 hemagglutinin antigen showed excellent humoral and cellular immunity, evoking high levels of antibodies and cytokines and inducing a great expansion of splenocytes in immunized mice. Also, the nanoadjuvant combined with ovalbumin antigen led to a potent cytotoxic T-cell response, substantially inhibited tumor growth, and improved the survival rate of mice in a melanoma model. This study showed the universal performances of npCpG in infectious disease prevention and tumor immunotherapy to demonstrate the translational potential.

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Section: Resultsmentioning

confidence: 97%

Universal and Translational Nanoparticulate CpG Adjuvant

Qiao

Liu

et al. 2022

ACS Appl. Mater. Interfaces

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“…[9] Fortunately, the inadequacy of ICB-based immunotherapy can be remedied by synergistic therapy, which has brought an incredible revolution in cancer therapy. [10] For example, Yan et al designed an aggregation-induced emission reagent (TPA-BT-DPTQ)-mediated PTT to eliminate primary tumors and boost immunogenicity. Synergistic PTT and PD-L1 antibody successfully avoided metastasis and recurrence of cancer.…”

Section: Introductionmentioning

confidence: 99%

A Noble AuPtAg‐GOx Nanozyme for Synergistic Tumor Immunotherapy Induced by Starvation Therapy‐Augmented Mild Photothermal Therapy

et al. 2022

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Notwithstanding immune checkpoint blocking (ICB) therapy has made eminent clinical breakthroughs, overcoming immunologically “cold” tumors remains challenging. Here, a cascade potentiated nanomodulator AuPtAg‐GOx is engineered for boosting immune responsiveness. Upon 1064 nm laser irradiation, AuPtAg‐mediated mild photothermal therapy (PTT) activates cytotoxic T lymphocytes and reverses the immunogenic “cold” tumor microenvironment. Further, to amplify the thermal sensitivity of tumor cells, glucose oxidase (GOx) is introduced to suppress the production of heat shock proteins, thereby promoting mild photothermal therapy. Complementarily, AuPtAg nanozymes with catalase‐like activity can ameliorate tumor hypoxia, significantly improving the GOx activity. As a result, the combination of AuPtAg‐GOx with self‐augmented photothermal ability and PD‐L1 antibody can further escalate the antitumor efficacy. The AuPtAg‐GOx‐based synergistic starvation therapy, mild PTT, and immunotherapy cascade enhancement therapy strategy can be a favorable tool to effectively kill cancer cells.

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“…It is worth noting that different administration methods face different immune environments. (4) Adjuvants can be delivered more precisely and with greater stability using nanomedicine platform [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Self-adjuvanting cancer nanovaccines

Liao

Huang

et al. 2022

J Nanobiotechnol

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Nanovaccines, a new generation of vaccines that use nanoparticles as carriers and/or adjuvants, have been widely used in the prevention and treatment of various diseases, including cancer. Nanovaccines have sparked considerable interest in cancer therapy due to a variety of advantages, including improved access to lymph nodes (LN), optimal packing and presentation of antigens, and induction of a persistent anti-tumor immune response. As a delivery system for cancer vaccines, various types of nanoparticles have been designed to facilitate the delivery of antigens and adjuvants to lymphoid organs and antigen-presenting cells (APCs). Particularly, some types of nanoparticles are able to confer an immune-enhancing capability and can themselves be utilized for adjuvant-like effect for vaccines, suggesting a direction for a better use of nanomaterials and the optimization of cancer vaccines. However, this role of nanoparticles in vaccines has not been well studied. To further elucidate the role of self-adjuvanting nanovaccines in cancer therapy, we review the mechanisms of antitumor vaccine adjuvants with respect to nanovaccines with self-adjuvanting properties, including enhancing cross-presentation, targeting signaling pathways, biomimicking of the natural invasion process of pathogens, and further unknown mechanisms. We surveyed self-adjuvanting cancer nanovaccines in clinical research and discussed their advantages and challenges. In this review, we classified self-adjuvanting cancer nanovaccines according to the underlying immunomodulatory mechanism, which may provide mechanistic insights into the design of nanovaccines in the future. Graphical Abstract

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Two‐Pronged Intracellular Co‐Delivery of Antigen and Adjuvant for Synergistic Cancer Immunotherapy

Cited by 59 publications

References 60 publications

Universal and Translational Nanoparticulate CpG Adjuvant

Universal and Translational Nanoparticulate CpG Adjuvant

A Noble AuPtAg‐GOx Nanozyme for Synergistic Tumor Immunotherapy Induced by Starvation Therapy‐Augmented Mild Photothermal Therapy

Self-adjuvanting cancer nanovaccines

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