MDR GENE THERAPY FOR DRUG RESISTANCE IN BREAST CANCER CLINICAL TRIALS

这项捐赠的目标是传递和表达人类的多重 CD34+造血祖细胞耐药基因的研究 对晚期乳腺癌患者使用安全有效的 逆转录病毒。这种治疗的预计结果是MDR转导 细胞将改善后续化疗的骨髓抑制 被MDR灭活的药物(蒽环类、长春花碱、 依托泊苷和紫杉醇)。正常的HPC具有低水平的MDR活性， 因此，对这些药物优先敏感。如果成功，这将是 该计划将为慢性阻塞性肺疾病患者的治疗增加新的模式 晚期乳腺癌以及解决亲属的问题 骨髓、外周血祖细胞(PBPC)和 内源性造血促进骨髓恢复。随后的研究将 评估更高剂量的单一药物而不是联合化疗方案 利用重复剂量的受多药耐药影响的药物。协议将是 开发和实施将使用MDR基因转移的药物。这个 临床计划的目标是执行和监督批准的 协议，并执行后续阶段1和2协议 BCTG与CTEP合作。新的协议将专注于 MDR最佳的外周血祖细胞的转导 逆转录病毒载体及转导CD34+细胞的最佳条件。 随后的研究将通过设计和开发这些观察结果 评估受多药耐药影响的药物组合的重复剂量 有多药耐药转导造血祖细胞的患者 含有逆转录病毒的。

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.