Toward translation of a plant virus-based in situ vaccination nanotechnology

基于植物病毒的原位疫苗接种纳米技术的转化

• 批准号: 10529016
• 负责人: STEVEN FIERING
• 金额: $ 64.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-22 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10529016
• 关键词: Abscopal effect; Antigens; Antitumor Response; Applications Grants; Award; Biodistribution; Biological; Biological Markers; Biopsy; Biotechnology; Blood; Cancer Intervention; Canis familiaris; Cells; Chemistry; Chromatography; Chronic; Clinical; Clinical Trials; Companions; Cowpea Mosaic Viruses; Data; Development; Disease remission; Dose; Enrollment; Evaluation; Fabaceae; Feces; Formulation; Foundations; Funding; Future; Genomics; Goals; Human; Image; Immune; Immune system; Immunologic Memory; Immunologics; Immunosuppression; Immunotherapy; Industry Standard; Inflammation; Injections; Innate Immune System; Intellectual Property; Investigation; Investigational Therapies; Leadership; Malignant Neoplasms; Mammals; Mast Cell Neoplasm; Mediating; Methodology; Methods; Modeling; Molecular; Monitor; Mosaicism; Mus; Nanotechnology; Neoplasm Metastasis; Oncogenic Viruses; Oncology; Organ; Patients; Pharmacology; Pharmacology and Toxicology; Phase 0 Clinical Trial; Plant Viruses; Plants; Positioning Attribute; Production; Protocols documentation; Recurrence; Safety; Site; Structure; Techniques; Technology; Time; Toxic effect; Toxicology; Translating; Translational Research; Translations; Tumor Antigens; Tumor Burden; Tumor Immunity; Tumor Markers; Urine; Vaccine Therapy; anti-tumor immune response; arm; base; cancer immunotherapy; cell killing; clinical practice; drug candidate; experience; immunoengineering; immunotherapy trials; improved; in situ vaccination; in situ vaccine; intervention program; malignant breast neoplasm; melanoma; method development; mouse model; nanoparticle; neoantigens; neoplastic cell; oncology trial; patient subsets; personalized approach; prevent; programs; recruit; residence; sarcoma; success; systemic toxicity; treatment response; tumor; tumor immunology; tumor microenvironment; vaccine candidate

Summary This R01, submitted to the Toward Translation of Nanotechnology Cancer Interventions (TTNCI) program, is a continuation of our successful U01 CA218292 (09/2017-07/2022), funded through the NCI Alliance for Nanotechnology in Cancer program. During the U01 project period, we demonstrated that our nanoparticles derived from the plant virus cowpea mosaic virus (CPMV) stimulate a potent antitumor immune response against multiple tumor mouse models. Additionally, trials in companion dogs with melanoma, sarcoma, and breast cancer demonstrate potent antitumor efficacy with our unique immunotherapy approach. CPMV is an intratumoral injected in situ vaccine (ISV) technology, with an ability to induce durable immune-mediated antitumor efficacy against treated and untreated tumors as well as immunological memory against recurrence. Mechanistically, CPMV activates the innate immune system to improve processing of tumor-associated and neoantigens, thereby resulting in a more functional adaptive antitumor immunity against antigens expressed by the tumor. This results in remissions of treated and untreated malignant tumors, and protection from recurrence via the adaptive arm and immune memory. Building on this strong foundation of data as well as intellectual property, this project will focus on optimizing GMP manufacturing and pharmacology in murine tumor models and canine patients to provide the foundational basis of future human oncology trials. The multi-PI leadership team Steinmetz (UC San Diego), Fiering (Dartmouth) and Ranjan (OSU) brings complimentary expertise in plant virus-based CPMV nanotechnology, cancer immunology, and veterinary oncology/immunotherapy trials. Our team is also supported by a group of consultants with expertise in regulatory (Garnick, Mosaic IE Inc.), pharmacology/toxicology (Luksic, Intrinsik), clinical (Garovoy, Mosaic IE Inc.) affairs, as well as experience in vertical farming (Eisenberg, OPO). We believe that our strong team of collaborators can help establish the future manufacture of the plant-derived biologic. We will fulfil the following Specific Aims: (1) Chemistry, Manufacturing, and Control (CMC) method development for scalable manufacture and QAC of the CPMV- ISV, (2) Pharmacology: Determine biodistribution, dosing, and toxicology of the CPMV-ISV drug candidate in orthotopic and metastatic mouse models of melanoma; and (3) Canine trials: establish dosing and safety in canine oncology trials in varying tumor types amenable for in situ vaccination (melanoma, sarcoma, and mast- cell tumor). Through parallel trials in murine tumor models and dog patients, we will identify biopsy or blood biomarkers for longitudinal monitoring of treatment response. Successful completion would position us for good manufacturing practice (GMP) production of this plant virus-based biologic nanotechnology and to continue the developmental path, e.g. through the NCI Experimental Therapeutics (NExT) program, thereby translating the CPMV-based drug candidate into a human clinical trial and practice.

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