A NOVEL ADJUVANT FOR TUMQR VACCINATION

描述（由申请人提供）：在美国和许多其他国家，癌症仍然是导致死亡的主要原因。当肿瘤细胞没有被免疫系统发现或消灭时，癌症就会在体内发展和扩散。虽然某些新疗法有希望，但目前的癌症治疗，包括化疗和放疗，往往会非选择性地杀死细胞，并可能对患者造成伤害。因此，至关重要的是开发免疫治疗方法，使患者的免疫系统能够识别癌细胞并消灭它们。与现有的治疗方法相比，免疫疗法的优势在于对肿瘤的免疫反应是特异性的、安全的，并且具有记忆成分，可以保护身体免受新出现的肿瘤的侵害。针对肿瘤抗原的t细胞反应是预防和消除癌细胞的关键。T细胞需要三种不同的信号来激活；信号1是抗原特异性的，由t细胞受体与抗原相互作用介导，信号2由受体和配体相互作用介导，如CD40/CD40L和CD28/B7，信号3由细胞因子介导。缺乏信号2或共刺激是许多肿瘤逃避免疫系统的关键机制。在这项应用中，我们建议使用一种名为ProtExTM的专有技术，在不到2小时的时间内将一种新的共刺激蛋白SA-hCD40L放置在卵巢肿瘤细胞表面。当这种蛋白出现在肿瘤细胞表面时，有望激活患者免疫系统的关键细胞，从而产生抗肿瘤反应。这可能导致肿瘤细胞的物理消除，甚至在身体的远处。在本项目中，我们将在卵巢来源的人肿瘤细胞表面展示SA-hCD40L，并测试这些细胞是否能在健康个体和卵巢癌患者的外周血淋巴细胞中产生抗肿瘤免疫反应。这种方法的体外概念验证将使我们能够在临床中测试这种方法对癌症免疫治疗的功效。从长远来看，我们将开发和销售含有SA-hCD40L的抗肿瘤疫苗。使用这种疫苗将降低死亡率，提高癌症患者的生活质量。这个项目的长期成功将带来更有效的癌症治疗方法，同时保护病人的整体健康

DESCRIPTION (provided by applicant): Cancer continues to be a leading cause of death in the U.S. and in many other countries. Cancers develop and spread within the body when tumor cells are not detected or destroyed by the immune system. Although certain new therapies hold promise, current cancer treatments, including chemotherapy and radiation therapy, tend to kill cells non-selectively and can cause harm to the patient. It is, therefore, critical to develop immunotherapeutic approaches that will enable the patient's immune system to recognize the cancer cells and eliminate them. The advantage of immunotherapy over the existing treatment approaches is that immune response to tumors is specific, safe, and has a memory component that can safeguard the body against newly arising tumors. T-cell response directed at tumor antigens is critical to the prevention and elimination of cancer cells. T cells require three distinct signals for activation; Signal 1 is antigen specific and mediated by the T-cell receptor interaction with the antigen, Signal 2 is mediated by receptor and ligand interactions, such as CD40/CD40L and CD28/B7, and Signal 3 is mediated by cytokines. Lack of signal 2 or co-stimulation is a critical mechanism used by many tumors for the evasion of the immune system. In this application, we propose to use a proprietary technology called ProtExTM to place a novel costimulatory protein, SA-hCD40L, on the surface of ovarian tumor cells in less than 2 hours. When present on the tumor cell surface, the protein is expected to activate key cells of the patient's immune system to mount an anti-tumor response. This may result in physical elimination of tumor cells, even at distant sites in the body. During this project we will display SA-hCD40L on the surface of human tumor cells of ovarian origin and test whether these cells can generate anti-tumor immune responses in peripheral blood lymphocytes harvested from healthy individuals and ovarian cancer patients. In vitro proof-of-concept for this approach will allow us to test the efficacy of this approach for cancer immunotherapy in the clinic. In the longer term, we will develop and market an anti-tumor vaccine containing SA-hCD40L. Use of the vaccine will lower the death rate and improve the quality of life of cancer patients. The long-term success of this project will lead to more effective treatment of cancer in a way that preserves the patient's overall health