IMMUNIZATION AGAINST MELANOMA DIFFERENTIATION ANTIGENS

针对黑色素瘤分化抗原的免疫接种

• 批准号: 6624663
• 负责人: ALAN N. HOUGHTON
• 金额: $ 25.48万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6624663
• 关键词: MHC class II antigen; antigen presentation; autoimmunity; cytotoxic T lymphocyte; differentiation antigens; disease /disorder model; genetically modified animals; helper T lymphocyte; laboratory mouse; melanoma; monophenol monooxygenase; neoplasm /cancer immunology; neoplastic process; tissue /cell culture

Self-antigens, in the form of differentiation antigens, are commonly recognized on melanoma and other cancers by the immune system. It has been unclear whether recognition of these antigens is relevant to immunity to cancer. The tyrosinase family has emerged as prototypes of differentiation antigens on human cancers. We actually do not know very much about immune recognition of these antigens, or other differentiation antigens. Recognition of these antigens presents many problems. First, how is recognition of these antigens possible in the face of immune tolerance. Second, even when recognition is possible, can this generate immunity that can reject cancer. Finally, if immunity to differentiation antigens can reject cancer, what are the potential autoimmune sequelae. We have used a mouse melanoma model to show that mice can be tolerant to tyrosinase family antigens. Tolerance can be broken by immunization wit altered forms of antigen. This can generate antibody and CD8+ T cell responses that are capable of rejecting tumors. CD4+ cells are required for immunity. Our aims are to: 1) Investigate how cancer immunity is uncoupled from autoimmunity; 2) Investigate the role of CD4+ T cell responses in tumor immunity against differentiation antigens.; and 3) Develop mouse models that develop endogenous invasive melanomas and study immunity against differentiation antigens at different steps in tumor progression.

自身抗原以分化抗原的形式在黑色素瘤和其他癌症上通常被免疫系统识别。目前尚不清楚这些抗原的识别是否与癌症免疫力相关。酪氨酸酶家族已成为人类癌症分化抗原的原型。事实上，我们对这些抗原或其他分化抗原的免疫识别知之甚少。这些抗原的识别存在许多问题。首先，面对免疫耐受，如何识别这些抗原。第二，即使识别是可能的，这是否可以产生免疫力，可以拒绝癌症。 最后，如果对分化抗原的免疫可以排斥癌症，那么潜在的自身免疫后遗症是什么。我们已经使用小鼠黑色素瘤模型来显示小鼠可以耐受酪氨酸酶家族抗原。用改变形式的抗原进行免疫可以打破耐受性。这可以产生能够排斥肿瘤的抗体和CD 8 + T细胞应答。CD 4+细胞是免疫所必需的。我们的目标是：1）研究癌症免疫是如何从自身免疫中解耦的; 2）研究CD 4 + T细胞应答在肿瘤免疫中对分化抗原的作用。和3）开发发展内源性侵袭性黑素瘤的小鼠模型，并研究在肿瘤进展的不同阶段针对分化抗原的免疫。