Particulate carrier systems as adjuvants for cancer vaccines

Saung, May Tun; Ke, Xiyu; Howard, Gregory P.; Li, Zheng; Mao, Hai‐Quan

doi:10.1039/c9bm00871c

Cited by 19 publications

(18 citation statements)

References 134 publications

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“…Nanoparticles and microparticles have emerged as a powerful vaccine delivery system by increasing uptake of the target antigen at specific sites or by activating specific antigen presenting cell (APC) populations, such as dendritic cells [ 6 ]. Particle properties such as size, surface characteristics, and composition can be manipulated to promote different types of antigen presentation and cellular uptake, as well as subsequent immune responses [ 7 ]. For example, polystyrene nanoparticles (PS NPs) in the 40–50 nm viral size range elicit high levels of CD4+ and CD8+ T-cells, and long-lasting antibody responses [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

et al. 2020

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Sustained immune responses, particularly antibody responses, are key for protection against many endemic infectious diseases. Antibody responses are often accompanied by T helper (Th) cell immunity. Herein we study small biodegradable poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) nanoparticles (PEG-b-PLGA NPs, 25–50 nm) as antigen- or adjuvant-carriers. The antigen carrier function of PEG-b-PLGA NPs was compared against an experimental benchmark polystyrene nanoparticles (PS NPs, 40–50 nm), both conjugated with the model antigen ovalbumin (OVA-PS NPs, and OVA-PEG-b-PLGA NPs). The OVA-PEG-b-PLGA NPs induced sustained antibody responses to Day 120 after two immunizations. The OVA-PEG-b-PLGA NPs as a self-adjuvanting vaccine further induced IL-4 producing T-helper cells (Th2), but not IFN-γ producing T-cells (Th1). The PEG-b-PLGA NPs as a carrier for CpG adjuvant (CpG-PEG-b-PLGA NPs) were also tested as mix-in vaccine adjuvants comparatively for protein antigens, or for protein-conjugated to PS NPs or to PEG-b-PLGA NPs. While the addition of this adjuvant NP did not further increase T-cell responses, it improved the consistency of antibody responses across all immunization groups. Together these data support further development of PEG-b-PLGA NPs as a vaccine carrier, particularly where it is desired to induce Th2 immunity and achieve sustained antibody titers in the absence of affecting Th1 immunity.

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Section: Introductionmentioning

confidence: 99%

Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

et al. 2020

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“…Exogenous cytokines, including IFN‐1, IL‐12, and IL‐27, have also been considered, but are constrained by getting sufficient local activity without driving systemic toxicity. To address this, a multitude of nanoparticle formulations are under preclinical testing, 62 with many of these based on liposome scaffolds or particular aggregates. Both of these “vectors” can be delivered either passively (relying on the enhanced permeability and retention effect) or by active targeting with antibodies, ligands, or aptamers, in particular, targeting receptors on DCs, such as DEC‐205, Clec9a/DNGR, and the mannose receptor.…”

Section: A Role For Cancer Vaccines In the Future Immunotherapy Repermentioning

confidence: 99%

Fundamentals of Cancer Immunology and Their Application to Cancer Vaccines

Bullock

2020

Clinical Translational Sci

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The capacity of the immune system to influence tumor progression has been a long‐standing notion that first generated clinical traction over a 100 years ago when Dr. William Coley injected disaggregated bacterial components into sarcomas and noted that the ensuing inflammation commonly associated with tumor regression. 1 Since then, our understanding of the individual components and the overall interaction of the immune system has expanded exponentially. This has led to the development of a robust understanding of how components of innate and adaptive immunity recognize and respond to tumors and leveraging this information for the development of tumor immunotherapies. However, clinical failures have also deepened our knowledge of how tumors might adapt/be selected to avoid or inhibit immune responses, which, in turn, has led to the further iteration of immunotherapies. In this tutorial, the established elements of tumor immunity are explained, and areas where our knowledge base is too thin is highlighted. The principles of tumor immunity that guide the development of cancer vaccines are further illustrated, and potential considerations of how to integrate cancer vaccines with conventional therapies and other immunotherapies are proposed.

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“…The use of nanoparticle-based formulations has shown promise to improve antigen delivery. [13][14][15][16][17][18][19][20][21][22] On the one hand, the nanoparticle carrier helps to prevent premature degradation of the antigen. In addition, by tailoring size and surface chemistry, nanoparticle-based carriers can also allow targeted delivery to, and augment antigen uptake by dendritic cells.…”

Section: Introductionmentioning

confidence: 99%

Polymer Nanoparticle‐Mediated Delivery of Oxidized Tumor Lysate‐Based Cancer Vaccines

Berti

Graciotti

Boarino

et al. 2021

Macromolecular Bioscience

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Cancer vaccination is a powerful strategy to combat cancer. A very attractive approach to prime the immune system against cancer cells involves the use of tumor lysate as antigen source. The immunogenicity of tumor lysate can be further enhanced by treatment with hypochlorous acid. This study explores poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the delivery of oxidized tumor lysate to dendritic cells. Using human donor-derived dendritic cells, it is found that the use of PLGA nanoparticles enhances antigen uptake and dendritic cell maturation, as compared to the use of the free tumor lysate. The ability of the activated dendritic cells to stimulate autologous peripheral blood mononuclear cells (PBMCs) is assessed in vitro by coculturingPBMCs with A375 melanoma cells. Live cell imaging analysis of this experiment highlights the potential of nanoparticle-mediated dendritic-cell-based vaccination approaches. Finally, the efficacy of the PLGA nanoparticle formulation is evaluated in vivo in a therapeutic vaccination study using B16F10 tumor-bearing C57BL/6J mice. Animals that are challenged with the polymer nanoparticle-based oxidized tumor lysate formulation survive for up to 50 days, in contrast to a maximum of 41 days for the group that receives the corresponding free oxidized tumor lysate-based vaccine.

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Particulate carrier systems as adjuvants for cancer vaccines

Abstract: Particulate systems including nanoparticles and microparticles show great potential as carriers for antigen and adjuvant delivery in cancer vaccine development.

Cited by 19 publications

References 134 publications

Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

Fundamentals of Cancer Immunology and Their Application to Cancer Vaccines

Polymer Nanoparticle‐Mediated Delivery of Oxidized Tumor Lysate‐Based Cancer Vaccines

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