Synthesis of Glycopeptide-Based Cancer Antigen Vaccines

糖肽癌抗原疫苗的合成

• 批准号: 8101525
• 负责人: Steven Sucheck
• 金额: $ 33.47万
• 依托单位: UNIVERSITY OF TOLEDO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8101525
• 关键词: Acids; Active Immunotherapy; Adjuvant; Antibodies; Antibody Formation; Antigen-Presenting Cells; Antigens; Autologous; Biological Markers; Breast Cancer Cell; CD4 Positive T Lymphocytes; Cancer Vaccines; Carbohydrates; Chemicals; Cholesterol; Conjugate Vaccines; Dendritic Cells; Diagnostic; Drug Formulations; Encapsulated; Ficoll; Flow Cytometry; Glycoconjugates; Glycopeptides; Helper-Inducer T-Lymphocyte; High Pressure Liquid Chromatography; Human; Humor; Immune response; Immunization; Immunoglobulin G; Immunoglobulin M; Immunology; Link; Liposomes; Literature; MCF7 cell; Malignant Neoplasms; Mediating; Methodology; Methods; Mucin-1 Staining Method; Mus; Neoplasm Metastasis; Oligosaccharides; Organic Chemistry; Ovalbumin; Peptide Synthesis; Peptides; Phase; Receptors, Antigen, B-Cell; Serum; Solid; Surface; T-Cell Proliferation; T-Lymphocyte; T-Lymphocyte Epitopes; Therapeutic Agents; Training; Tumor-Associated Carbohydrate Antigens; Vaccine Antigen; Vaccines; Xenobiotics; base; cancer cell; cancer recurrence; cancer therapy; immunogenicity; in vivo; interest; light scattering; monophosphoryl lipid A; response; single molecule

DESCRIPTION (provided by applicant): Tumor-associated carbohydrate antigens (TACAs) are saccharides and oligosaccharides which show highly restricted expression on cancer cells. Since TACAs are unique to cancer cells, there is a great interest in generating an active immune response against TACAs as a means of reducing cancer metastasis or recurrence. TACAs are also useful biomarkers for evaluating the aggressiveness of the cancer. Two major challenges to using TACAs in active immunotherapy are their poor antigenicity and the inherent difficulty of synthesizing oligosaccharides and related glycoconjugates by chemical means. This application proposes to synthesize and study the antigenicity of TACA glycoconjugates. A key aspect of the proposal is the study of increased vaccine antigenicity mediated by xenobiotic carbohydrates unrelated to the TACAs. The xenobiotic carbohydrates are proposed to enhance antigenicity through anti- carbohydrate antibody-mediated mechanisms. This proposal takes advantage of a collaborative interaction between PIs trained in organic chemistry and immunology so that the antigenicity of all vaccines will be well characterized in mice. PUBLIC HEALTH RELEVANCE: This project will develop and evaluate the cellular and humor immune response of vaccines in mice that will serve as leads for human anti-cancer vaccines. Chemical approaches will be developed that will aid in generating diagnostic and therapeutic agents for the treatment of cancer.

描述（由申请方提供）：肿瘤相关碳水化合物抗原（TACA）是在癌细胞上表现出高度限制性表达的寡糖。由于TACA对癌细胞是独特的，因此产生针对TACA的主动免疫应答作为减少癌症转移或复发的手段具有很大的兴趣。TACA也是用于评估癌症侵袭性的有用生物标志物。在主动免疫治疗中使用TACA的两个主要挑战是它们的抗原性差和通过化学手段合成寡糖和相关糖缀合物的固有困难。本申请提出合成并研究TACA糖缀合物的抗原性。该提案的一个关键方面是研究与TACA无关的外源性碳水化合物介导的疫苗抗原性增加。提出异生质碳水化合物通过抗碳水化合物抗体介导的机制增强抗原性。该提案利用了在有机化学和免疫学方面受过培训的PI之间的协作互动，以便在小鼠中很好地表征所有疫苗的抗原性。 公共卫生相关性：该项目将在小鼠中开发和评估疫苗的细胞和体液免疫应答，这些免疫应答将作为人类抗癌疫苗的先导。将开发化学方法，以帮助产生用于治疗癌症的诊断和治疗剂。