An integrated polymeric carrier for subunit cancer vaccines

用于亚单位癌症疫苗的集成聚合物载体

• 批准号: 10576958
• 负责人: Suzie H. Pun
• 金额: $ 47.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576958
• 关键词: Acceleration; Address; Adjuvant; Amino Acid Sequence; Antigen Presentation; Antigen Targeting; Antigen-Presenting Cells; Antigens; Binding; Bioinformatics; Biological Assay; Breast Cancer Model; CAR T cell therapy; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Vaccines; Cancerous; Chemistry; Clinical; Clinical Trials; Cross Presentation; Cytosol; Dendritic Cells; Dendritic cell activation; ERBB2 gene; Endosomes; Engineering; Epitopes; Evaluation; Excretory function; Formulation; Goals; Immune checkpoint inhibitor; Immune response; Immune system; Immunity; Immunologic Stimulation; Immunologics; Immunooncology; Immunosuppression; Immunotherapy; In Situ; In Vitro; Integrated Delivery Systems; Intravenous; Kinetics; Lead; Ligands; Malignant Neoplasms; Mammary Neoplasms; Mediating; Modeling; Mus; Nucleic Acids; Pathway interactions; Peptide Vaccines; Peptides; Polymers; Preclinical Testing; Predisposition; Prodrugs; Proteins; Recombinant Cytokines; Rejuvenation; Research; Risk; Safety; Structure; System; T cell response; T-Cell Activation; T-Lymphocyte Epitopes; Technology; Testing; Therapeutic; Time; Tissues; Toxic effect; Transgenic Mice; Translations; Tumor Antigens; Vaccination; Vaccine Adjuvant; Vaccines; anti-cancer; cancer immunotherapy; cancer prevention; cancer therapy; cancer type; clinical development; clinical efficacy; combat; controlled release; density; design; efficacy evaluation; extracellular; immunogenic; improved; in vivo; innovation; interest; lymph nodes; lymphatic vessel; manufacture; melanoma; monomer; neoantigens; peptide based vaccine; polymerization; prevent; prophylactic; research clinical testing; resiquimod; subcutaneous; success; synergism; systemic toxicity; trafficking; tumor; tumor growth; vaccine access; vaccine delivery; vaccine development; vaccine efficacy; vaccine formulation

PROJECT SUMMARY Cancer vaccines are a promising immuno-oncology approach that can elicit highly tumor-specific responses from the immune system, resulting in prolonged anti-cancer protection. Peptide-based vaccines are especially attractive because they have low toxicity risk and can be produced easily at large scale with good storage stability. However, peptide antigens are inherently poorly immunogenic and susceptible to rapid degradation and excretion after administration. Thus, the success of peptide-based cancer vaccines are critically tied to their effective formulation and delivery. The ideal peptide vaccine formulation would replicate each of these critical aspects: recognition and internalization by dendritic cells, activation of these dendritic cells, and antigen delivery to both MHC I (called cross-presentation) and MHC II molecules. In this application, we propose to develop a polymer-based peptide antigen carrier that uniquely addresses all of the aforementioned delivery needs in a well-controlled, scalable system through the integration of targeting ligands, controlled release adjuvants, and cytosolic and lysosomal antigen delivery mechanisms. Our main objectives are to 1) optimize polymer structure and synthesis through material engineering, 2) assess peptide and adjuvant delivery and characterize in vitro and in vivo trafficking and delivery, 3) optimize formulations for vaccine efficacy in a murine melanoma model and 4) evaluate efficacy and safety in a murine breast cancer model for cancer prevention and therapy. Successful completion of these aims will lead to a formulation poised for GMP manufacturing and the IND pathway toward clinical testing.

项目总结