Targeting a Poor Prognosis Marker for Tumor Therapy

描述（由申请人提供）： 针对肿瘤治疗的不良预后标志物概述本提案的目的是开发用于消除转移性癌症的医学治疗。根据美国国家癌症研究所的数据，近年来许多类型癌症的存活率有所提高;然而，它仍然是美国第二大死亡原因。该提案描述了一种实验设计，以验证basigin-2（也称为CD 147或EMMPRIN）作为创新肿瘤治疗的细胞表面靶标的适用性。该项目将在确定basigin-2对进一步药物开发的适用性方面实现重要目标：1）通过使用basigin-2的抗体提供靶部分（basigin-2）内化的证据，以及2）证明具有特异性，无论是在靶向肿瘤的能力方面还是在正常（较低水平）表达方面，抗basigin对靶点具有特异性。在该I期授权中，将产生具有两种组分的细胞毒素：1）特异性靶向并内化到basigin-2阳性细胞中的抗basigin，和2）在被抗体内化后将抑制蛋白质合成的毒素。这种创新的方法将创造一种靶向肿瘤细胞、转移和血管生成的分子，其想法不仅是减缓肿瘤细胞增殖，而且是消除肿瘤。 公共卫生相关性： 该项目通过靶向在许多预后不良的肿瘤类型的表面上表达的分子，为广泛的致命癌症的潜在治疗开辟了新的方向。虽然提出通过靶向分子basigin-2直接靶向这些肿瘤，但也表明靶向肿瘤转移和血管生成，因为basigin-2在这些危险过程中起重要作用。该项目建立在现有技术的基础上，但将几种技术结合在一起，朝着一个新的创新方向发展。

DESCRIPTION (provided by applicant): Targeting a Poor Prognosis Marker for Tumor Therapy Summary The purpose of this proposal is to develop a medical treatment for the elimination of metastatic cancers. According to the National Cancer Institute, the survival rate for many types of cancer has improved in recent years; however, it is still the second leading cause of death in the United States. This proposal describes an experimental design to verify the suitability of basigin-2 (also known as CD147 or EMMPRIN) as a cell surface target for an innovative tumor therapy. This project will accomplish important goals in determining the suitability of basigin-2 for further drug development: 1) Provide proof of internalization of the target moiety (basigin-2) by using an antibody to basigin-2, and 2) Demonstrate that there is specificity, both in terms of greater ability to target the tumor over normal (lower level) expression and that anti-basigin is specific for the target. In this Phase I grant, a cytotoxin will be produced that has two components: 1) anti-basigin to specifically target and internalize into basigin-2 positive cells, and 2) a toxin that will inhibit protein synthesis upon internalization by the antibody. This innovative approach will create a molecule that targets tumor cells, metastasis and angiogenesis, with the idea to not just slow tumor cell proliferation, but to eliminate tumors. PUBLIC HEALTH RELEVANCE: Targeting a Poor Prognosis Marker for Tumor Therapy Narrative This project begins a new direction of potential treatment for a wide range of deadly cancers by targeting a molecule that is expressed on the surface of many tumor types with poor prognosis. While it is proposed to directly target these tumors through targeting the molecule, basigin-2, targeting of tumor metastasis and angiogenesis is also indicated, since basigin-2 plays important roles in those dangerous processes. The project builds on current technologies, but puts several together to go in a new, innovative direction.