DNA Vaccination Against Melanoma

但前提是。 癌症患者的免疫系统识别癌症上的自身抗原。免疫反应 在实验室模型中，自身抗原可导致癌症排斥反应。针对这些抗原的免疫 然而，这会带来问题，因为这些都是弱抗原。本提案解决了 目前针对自身抗原的分子定义的癌症疫苗：1)效力不足，2)特异性 仅限于单个表位或决定簇，以及3)需要调节免疫系统以支持对 接种疫苗。使用酪氨酸酶家族的原型分化抗原建立模型， 将研究多个异位表位和操纵蛋白质的稳定性和运输，以增加 抗癌自身抗原主动免疫的效力。在第一个目标中，DNA疫苗旨在 引入多个异位表位并加强抗原的处理和呈递，然后 在实验室治疗模型中测试抗体和T细胞反应的诱导以及抗肿瘤 活动。第二个目标是研究通过以下途径提高疫苗免疫反应的策略 调节体内平衡免疫细胞的恢复。另一种策略是探索以两者为免疫靶点 主动免疫或主动与被动相结合的肿瘤自身抗原和肿瘤间质 免疫接种。第三个目标是研究与DNA疫苗接种相结合的免疫调节。 临床研究。最后一个目的是探索DNA疫苗联合抗癌自身抗原的作用。 在一项临床研究中，接种了针对肿瘤基质的疫苗。

PROVIDED. Self antigens are recognized on cancers by the immune system of patients with cancer. Immune responses to self antigens can lead to rejection of cancer in laboratory models. Immunization against these antigens presents problems, however, because these are weak antigens. This proposal addresses limitations of the present molecularly defined cancer vaccines targeting self-antigens: 1) insufficient potency, 2) specificity for only individual epitopes or determinants, and 3) a need to modulate the immune system to favor response to vaccination. Using prototypical differentiation antigens of the tyrosinase family for models, creation of multiple heteroclitic epitopes and manipulation of protein stability and trafficking will be studied to increase potency of active immunization against cancer self-antigens. In the first Aim, DNA vaccines are designed to introduce multiple heteroclitic epitopes and to enhance antigen processing and presentation, followed by testing in laboratory treatment models for induction of antibody and T-cell responses and for antitumor activity. The second Aim investigates strategies to increase immune responses to vaccination through modulation of homeostatic immune cell recovery. Another strategy is explored to immunological target both cancer self-antigens and tumor stroma through active immunization or combination of active and passive immunization. The third Aim investigates immune modulation in combination with DNA vaccination in a clinical study. Finally, the last Aim explores DNA vaccination against cancer self-antigens in combination with vaccination against tumor stroma in a clinical study.