Delivery of nanovaccine towards lymphoid organs: recent strategies in enhancing cancer immunotherapy

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With the in-depth exploration on cancer therapeutic nanovaccines, increasing evidence shows that the poor delivery of nanovaccines to lymphoid organs has become the culprit limiting the rapid induction of anti-tumor immune response. Unlike the conventional prophylactic vaccines that mainly form a depot at the injection site to gradually trigger durable immune response, the rapid proliferation of tumors requires an efficient delivery of nanovaccines to lymphoid organs for rapid induction of anti-tumor immunity. Optimization of the physicochemical properties of nanovaccine ( e.g., size, shape, charge, colloidal stability and surface ligands) is an effective strategy to enhance their accumulation in lymphoid organs, and nanovaccines with dynamic structures are also designed for precise targeted delivery of lymphoid organs or their subregions. The recent progress of these nanovaccine delivery strategies is highlighted in this review, and the challenges and future direction are also discussed.

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Neoantigens in cancer immunotherapy.

Ton N. Schumacher, Robert D. Schreiber (2015)

The clinical relevance of T cells in the control of a diverse set of human cancers is now beyond doubt. However, the nature of the antigens that allow the immune system to distinguish cancer cells from noncancer cells has long remained obscure. Recent technological innovations have made it possible to dissect the immune response to patient-specific neoantigens that arise as a consequence of tumor-specific mutations, and emerging data suggest that recognition of such neoantigens is a major factor in the activity of clinical immunotherapies. These observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens. Copyright © 2015, American Association for the Advancement of Science.

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Tumor-associated macrophages: from mechanisms to therapy.

Roy Noy, Jeffrey W Pollard (2014)

The tumor microenvironment is a complex ecology of cells that evolves with and provides support to tumor cells during the transition to malignancy. Among the innate and adaptive immune cells recruited to the tumor site, macrophages are particularly abundant and are present at all stages of tumor progression. Clinical studies and experimental mouse models indicate that these macrophages generally play a protumoral role. In the primary tumor, macrophages can stimulate angiogenesis and enhance tumor cell invasion, motility, and intravasation. During monocytes and/or metastasis, macrophages prime the premetastatic site and promote tumor cell extravasation, survival, and persistent growth. Macrophages are also immunosuppressive, preventing tumor cell attack by natural killer and T cells during tumor progression and after recovery from chemo- or immunotherapy. Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

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Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy.

Lena Kranz, Mustafa Diken, Heinrich Haas … (2016)

Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

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Author and article information

Contributors

Jing Hu: hujing10@zju.edu.cn

Lingxiao Zhang:

ORCID: http://orcid.org/0000-0002-7066-6065

zhanglx913@zju.edu.cn

Journal

Journal ID (nlm-ta): J Nanobiotechnology

Journal ID (iso-abbrev): J Nanobiotechnology

Title: Journal of Nanobiotechnology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-3155

Publication date (Electronic): 25 November 2021

Publication date PMC-release: 25 November 2021

Publication date Collection: 2021

Volume: 19

Electronic Location Identifier: 389

Affiliations

[1 ]Ningbo Clinical Research Center for Digestive System Tumors, Ningbo Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010 China

[2 ]Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010 China

[3 ]Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315010 China

[4 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, , Zhejiang University, ; Hangzhou, 310027 China

[5 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Hangzhou Global Scientific and Technological Innovation Center, , Zhejiang University, ; Hangzhou, 211200 China

[6 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, College of Pharmaceutical Sciences, , Zhejiang University, ; Hangzhou, 310058 China

Author information

Lingxiao Zhang http://orcid.org/0000-0002-7066-6065

Article

Publisher ID: 1146

DOI: 10.1186/s12951-021-01146-2

PMC ID: 8620195

PubMed ID: 34823541

SO-VID: bf0feaaa-ef03-443e-b97d-2a63b9556596

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 1 October 2021

Date accepted : 14 November 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 32101123

Award Recipient : Lingxiao Zhang

Funded by: Ningbo Clinical Research Center for Digestive System Tumors

Award ID: 2019A21003

Award Recipient : Ting Cai

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ScienceOpen disciplines: Biotechnology

Keywords: nanovaccine,cancer immunotherapy,lymphoid organ,vaccine delivery,immune barrier

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ScienceOpen disciplines: Biotechnology

Keywords: nanovaccine, cancer immunotherapy, lymphoid organ, vaccine delivery, immune barrier

Delivery of nanovaccine towards lymphoid organs: recent strategies in enhancing cancer immunotherapy

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Cancer Immunotherapy

Most cited references 107

Neoantigens in cancer immunotherapy.

Tumor-associated macrophages: from mechanisms to therapy.

Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy.

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