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Multi-Immune Agonist Nanoparticle Therapy Stimulates Type I Interferons to Activate Antigen-Presenting Cells and Induce Antigen-Specific Antitumor Immunity.
Levy, Elizabeth S; Chang, Ryan; Zamecnik, Colin R; Dhariwala, Miqdad O; Fong, Lawrence; Desai, Tejal A.
Afiliación
  • Levy ES; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94158, United States.
  • Chang R; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94158, United States.
  • Zamecnik CR; Department of Medicine, University of California San Francisco, San Francisco, California 94143, United States.
  • Dhariwala MO; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94158, United States.
  • Fong L; Department of Dermatology, University of California San Francisco, San Francisco, California 94143, United Stats.
  • Desai TA; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California 94143, United States.
Mol Pharm ; 18(3): 1014-1025, 2021 03 01.
Article en En | MEDLINE | ID: mdl-33541072
Cancer immunity is mediated by a delicate orchestration between the innate and adaptive immune system both systemically and within the tumor microenvironment. Although several adaptive immunity molecular targets have been proven clinically efficacious, stand-alone innate immunity targeting agents have not been successful in the clinic. Here, we report a nanoparticle optimized for systemic administration that combines immune agonists for TLR9, STING, and RIG-I with a melanoma-specific peptide to induce antitumor immunity. These immune agonistic nanoparticles (iaNPs) significantly enhance the activation of antigen-presenting cells to orchestrate the development and response of melanoma-sensitized T-cells. iaNP treatment not only suppressed tumor growth in an orthotopic solid tumor model, but also significantly reduced tumor burden in a metastatic animal model. This combination biomaterial-based approach to coordinate innate and adaptive anticancer immunity provides further insights into the benefits of stimulating multiple activation pathways to promote tumor regression, while also offering an important platform to effectively and safely deliver combination immunotherapies for cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Nanopartículas / Inmunidad Adaptativa / Inmunidad Innata / Células Presentadoras de Antígenos / Neoplasias Límite: Animals Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Nanopartículas / Inmunidad Adaptativa / Inmunidad Innata / Células Presentadoras de Antígenos / Neoplasias Límite: Animals Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos