MDR GENE THERAPY FOR DRUG RESISTANCE IN BREAST CANCER CLINICAL TRIALS

这项赠款的目的是转移和表达人类的多样性 CD34+造血祖细胞（HPC）的耐药（MDR）基因 晚期乳腺癌患者使用安全有效的 逆转录病毒 这种治疗的预期结果是， 细胞将改善随后化疗的骨髓抑制， 被MDR灭活的药物（蒽环类，长春花生物碱， 依托泊苷和紫杉醇）。 正常的HPC具有低水平的MDR活性， 因此，优先对这些药物敏感。 如果成功，这 该计划将增加一种新的方式来治疗患者， 晚期乳腺癌以及解决问题的相对 骨髓、外周血祖细胞（PBPC）和 内源性造血到骨髓恢复。 后续研究将 评价较高剂量的单药化疗方案，然后联合化疗方案 利用重复剂量的MDR影响剂。 方案将 开发并实施了MDR基因转移。 的 临床计划的目标是执行和监测这一批准的 第一阶段和第二阶段议定书， BCTG与CTEP合作。 新协议将重点关注 转导具有最佳MDR的外周血祖细胞（PBPC） 逆转录病毒载体和转导CD34+细胞的最佳条件。 随后的研究将利用这些观察结果， 评价MDR影响药物的重复剂量组合， 具有MDR转导的造血祖细胞的患者 含有逆转录病毒。

The objectives of this grant are to transfer and express the human multiple drug resistance (MDR) gene in CD34+ hematopoietic progenitor cells (HPCs) of patients with advanced breast cancer using a safe and efficient retrovirus. The projected result of this treatment is that MDR-transduced cells will ameliorate myelosuppression of subsequent chemotherapy with drugs that are inactivated by MDR (anthracyclenes, vinca alkaloids, etoposide and taxol). Normal HPCs have low levels of MDR activity and are, therefore, preferentially sensitive to these drugs. If successful, this program would add a novel modality to the treatment of patients with advanced breast cancer as well as address questions of the relative contributions of marrow, peripheral blood progenitor cells (PBPCs) and endogenous hematopoiesis to marrow recovery. Subsequent studies would evaluate higher dose single agent then combination chemotherapy regimens utilizing repetative doses of MDR affected agents. Protocols will be developed and carried out in which MDR gene transfer will be used. The goal of the clinical program is to carry out and monitor this approved protocol and to carry out subsequent phase 1 and 2 protocols developed by the BCTG in collaboration with CTEP. New protocols will focus on transduction of peripheral blood progenitor cells (PBPC) with the best MDR retroviral vectors and optimal conditions for transduction of CD34+ cells. Subsequent studies would exploit these observations by designing and evaluating repeated doses of combinations of MDR affected drugs for patients who have had hematopoietic progenitors transduced with MDR containing retrovirus.