Tyer C L, Vredenburgh J J, Heimer M, Peters W P, Bast R C
Duke University Bone Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina 27710, USA.
Clin Cancer Res. 1996 Jan;2(1):81-6.
Peripheral blood progenitor cells (PBPCs) are being used increasingly to provide hematopoietic support after intensive chemotherapy. However, many investigators have detected tumor cells contaminating PBPC collections. Methods that eliminate the tumor cells and spare the normal hematopoietic progenitor cells may improve the number of long-term, disease-free survivors after intensive chemotherapy. We developed an effective method using anti-breast cancer murine monoclonal antibodies (MoAbs) and immunomagnetic beads to eliminate a low percentage of breast cancer cells from PBPCs. We identified optimal anti-breast cancer MoAbs that react with membrane glycoproteins and conditions for selective removal of tumor cells. Using three anti-breast cancer MoAbs (260F9, 317G5, and 520C9) at 0.8 microgram/ml, a cell concentration of 2 x 10(8) cells/ml and a bead:total cell ratio of 0.75 beads:1 cell, we eliminated 3.3-4.8 (mean, 4.1) logs of tumor cells consistently from a model system with 1% breast cancer cells and 99% normal PBPCs. Similar levels of tumor cell elimination were obtained with three breast cancer cell lines. Colony-forming units were not affected adversely, with a mean recovery of 200% compared with the control. A clinical trial has begun that uses immunomagnetically purged, autologous bone marrow and PBPCs to support patients with metastatic breast cancer receiving high-dose chemotherapy.
外周血祖细胞(PBPCs)越来越多地被用于在强化化疗后提供造血支持。然而,许多研究者已经检测到肿瘤细胞污染PBPC采集物。消除肿瘤细胞并保留正常造血祖细胞的方法可能会增加强化化疗后长期无病生存者的数量。我们开发了一种有效的方法,使用抗乳腺癌鼠单克隆抗体(MoAbs)和免疫磁珠从PBPCs中消除低比例的乳腺癌细胞。我们确定了与膜糖蛋白反应的最佳抗乳腺癌MoAbs以及选择性去除肿瘤细胞的条件。使用浓度为0.8微克/毫升的三种抗乳腺癌MoAbs(260F9、317G5和520C9)、细胞浓度为2×10⁸细胞/毫升以及磁珠与总细胞比例为0.75磁珠:1个细胞,我们从含有1%乳腺癌细胞和99%正常PBPCs的模型系统中始终如一地消除了3.3 - 4.8(平均4.1)对数级的肿瘤细胞。三种乳腺癌细胞系也获得了类似水平的肿瘤细胞消除效果。集落形成单位未受到不利影响,与对照组相比平均回收率为200%。一项临床试验已经开始,该试验使用免疫磁珠净化的自体骨髓和PBPCs来支持接受大剂量化疗的转移性乳腺癌患者。