Bionanotechnology for vaccine design

Frey, Steven J.; Castro, Ana Hortência Fônseca; Arsiwala, Ammar; Kane, Ravi S.

doi:10.1016/j.copbio.2018.03.003

Cited by 25 publications

(11 citation statements)

References 45 publications

(77 reference statements)

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“…In principle, as with any therapeutic agent, the structure could have a significant influence on safety, efficacy, and potency (11)(12)(13)(14)(15). In the case of vaccines, the way in which multiple molecular components are formulated could have a major influence on the biodistribution and delivery to cells of the immune system, and on the activation of immunostimulatory pathways that ultimately lead to the priming and expansion of antigen-specific T cells (16,17). Nanoparticle vaccines, in particular, provide a way to enhance the delivery of immunostimulatory molecules to the immune system through benefits in biodistribution and codelivery of adjuvant and antigen to immune cells (18).…”

mentioning

confidence: 99%

Rational vaccinology with spherical nucleic acids

Wang

Qin

Yamankurt

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

139

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In the case of cancer immunotherapy, nanostructures are attractive because they can carry all of the necessary components of a vaccine, including both antigen and adjuvant. Herein, we explore how spherical nucleic acids (SNAs), an emerging class of nanotherapeutic materials, can be used to deliver peptide antigens and nucleic acid adjuvants to raise immune responses that kill cancer cells, reduce (or eliminate) tumor growth, and extend life in three established mouse tumor models. Three SNA structures that are compositionally nearly identical but structurally different markedly vary in their abilities to cross-prime antigen-specific CD8+ T cells and raise subsequent antitumor immune responses. Importantly, the most effective structure is the one that exhibits synchronization of maximum antigen presentation and costimulatory marker expression. In the human papillomavirus-associated TC-1 model, vaccination with this structure improved overall survival, induced the complete elimination of tumors from 30% of the mice, and conferred curative protection from tumor rechallenges, consistent with immunological memory not otherwise achievable. The antitumor effect of SNA vaccination is dependent on the method of antigen incorporation within the SNA structure, underscoring the modularity of this class of nanostructures and the potential for the deliberate design of new vaccines, thereby defining a type of rational cancer vaccinology.

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mentioning

confidence: 99%

Rational vaccinology with spherical nucleic acids

Wang

Qin

Yamankurt

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

139

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“…However, the underlying mechanism of how these changes facilitate antigen presentation and alter the tumor microenvironment (TME) remains unclear. Moreover, a major challenge in immunotherapeutic development is the selection of the appropriate vehicle for delivering both adjuvant and antigen (25), as the way components are formulated can significantly influence delivery to the immune system and thus activation of immunostimulatory pathways (26,27). Nanoscale therapeutics have shown promise in this regard, by enhancing antigen-presenting cell (APC) activation over mixtures of adjuvant and antigen (28).…”

mentioning

confidence: 99%

Tumor cell lysate-loaded immunostimulatory spherical nucleic acids as therapeutics for triple-negative breast cancer

Callmann

Cole

Kusmierz

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Highly heterogenous cancers, such as triple-negative breast cancer (TNBC), remain challenging immunotherapeutic targets. Herein, we describe the synthesis and evaluation of immunotherapeutic liposomal spherical nucleic acids (SNAs) for TNBC therapy. The SNAs comprise immunostimulatory oligonucleotides (CpG-1826) as adjuvants and encapsulate lysates derived from TNBC cell lines as antigens. The resulting nanostructures (Lys-SNAs) enhance the codelivery of adjuvant and antigen to immune cells when compared to simple mixtures of lysates with linear oligonucleotides both in vitro and in vivo, and reduce tumor growth relative to simple mixtures of lysate and CpG-1826 (Lys-Mix) in both Py230 and Py8119 orthotopic syngeneic mouse models of TNBC. Furthermore, oxidizing TNBC cells prior to lysis and incorporation into SNAs (OxLys-SNAs) significantly increases the activation of dendritic cells relative to their nonoxidized counterparts. When administered peritumorally in vivo in the EMT6 mouse mammary carcinoma model, OxLys-SNAs significantly increase the population of cytotoxic CD8+ T cells and simultaneously decrease the population of myeloid derived suppressor cells (MDSCs) within the tumor microenvironment, when compared with Lys-SNAs and simple mixtures of oxidized lysates with CpG-1826. Importantly, animals administered OxLys-SNAs exhibit significant antitumor activity and prolonged survival relative to all other treatment groups, and resist tumor rechallenge. Together, these results show that the way lysates are processed and packaged has a profound impact on their immunogenicity and therapeutic efficacy. Moreover, this work points toward the potential of oxidized tumor cell lysate-loaded SNAs as a potent class of immunotherapeutics for cancers lacking common therapeutic targets.

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“…However, this conceptual framework was limited to monospecific multivalent interactions between proteins of certain topologies and was also not practically implementable to quickly analyze and design a wide range of molecular systems [26][27][28][29] .…”

Section: Mainmentioning

confidence: 99%

MVsim: a toolset for quantifying and designing multivalent interactions

Bruncsics

Errington

Sarkar

2021

Preprint

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Arising through multiple binding elements, multivalency can specify the avidity, duration, cooperativity, and selectivity of biomolecular interactions, but quantitative prediction and design of these properties has remained challenging. Here we present MVsim, an application suite built around a configurational network model of multivalency to facilitate the quantification, design, and mechanistic evaluation of multivalent binding phenomena through a simple graphical user interface. To demonstrate the utility and versatility of MVsim, we first show that both monospecific and multispecific multivalent ligand-receptor interactions, with their noncanonical binding kinetics, can be accurately simulated. We then quantitatively predict the ultrasensitivity and performance of multivalent-encoded protein logic gates, evaluate the inherent programmability of multispecificity for selective receptor targeting, and extract rate constants of conformational switching for the SARS-CoV-2 spike protein and model its binding to ACE2 as well as multivalent inhibitors of this interaction. MVsim is freely available at https://sarkarlab.github.io/MVsim/.

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Bionanotechnology for vaccine design

Cited by 25 publications

References 45 publications

Rational vaccinology with spherical nucleic acids

Rational vaccinology with spherical nucleic acids

Tumor cell lysate-loaded immunostimulatory spherical nucleic acids as therapeutics for triple-negative breast cancer

MVsim: a toolset for quantifying and designing multivalent interactions

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