TUMOR IMMUNOTHERAPY UTILIZING UNIVERSAL ALLOGEN

利用通用同种异体进行肿瘤免疫治疗

• 批准号: 3493497
• 负责人: JAN GELIEBTER
• 金额: $ 3.18万
• 依托单位: ADVANCED RESEARCH SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1993-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3493497
• 关键词: MHC class I antigen; drug design /synthesis /production; flow cytometry; immune tolerance /unresponsiveness; isoantigen; laboratory mouse; neoplasm /cancer immunotherapy; recombinant DNA; tissue /cell culture; transfection; tumor antigens

Many cancer cells are immunogenic, but somehow fail to stimulate the immune system. Transfecting tumor cells with allogeneic MHC class I genes stimulates the immune system to both the alloantigen and the tumor specific antigen on the tumor cells, such that the immune system can destroy parental, nontransfected tumor cells. Thus, tumor allogenization represents an approach to tumor immunotherapy whereby the host immune system may be stimulated to break tolerance against the tumor. An engineered class I gene called DC was constructed by engineering 2 cysteines into the alpha 1 domain of the Kb gene, making it appear more stable and immunogenic. DC-transfected tumor cells can stimulate long- term, systemic immunity against nontransfected tumor cells. DC is allogeneic in C57BL/6 mice from which it was derived, indicating that it will be allogeneic in all strains of mice and is capable of allogenizing all tumors from all strains of mice. Thus, in a clinical situation, DC can be a single off the shelf reagent for the allogenization of tumor cells and immunotherapy of tumors. We propose to define the conditions for maximum immunological expression of DC and endogenous class I for use in tumor immunotherapy.

许多癌细胞是免疫原性的，但不知何故不能刺激免疫原性。 免疫系统 用同种异体MHC I类转染肿瘤细胞 基因刺激免疫系统对抗同种异体抗原和肿瘤 肿瘤细胞上的特异性抗原，这样免疫系统就可以 破坏亲代未转染的肿瘤细胞。 因此， 代表了一种肿瘤免疫治疗的方法， 系统可能被刺激以打破对肿瘤的耐受性。 通过工程化2构建了称为DC的工程化I类基因 半胱氨酸进入Kb基因的α 1结构域，使其看起来更 稳定且具有免疫原性。 DC转染的肿瘤细胞可以刺激长- 即针对未转染肿瘤细胞的系统免疫。 DC是 同种异体的C57 BL/6小鼠，它来自，表明它 将在所有品系的小鼠中是同种异体的，并且能够同种异体化 所有品系小鼠的所有肿瘤。 因此，在临床情况下，DC 可以是用于肿瘤同种异体化的单一现成试剂 细胞和肿瘤的免疫治疗。 我们建议定义条件 用于DC和内源性I类的最大免疫学表达， 在肿瘤免疫治疗中。