Coombes R C, Buckman R, Forrester J A, Shepherd V, O'Hare M J, Vincent M, Powles T J, Neville A M
Cancer Res. 1986 Aug;46(8):4217-20.
We have devised a method utilizing a monoclonal antibody-toxin conjugate (LICR-LON-Fib75/abrin A-chain) for ridding bone marrow of infiltrating breast cancer cells to rescue patients with autologous bone marrow following high dose therapy. Initially we examined the activity of this conjugate in vitro. Five of seven human breast cancer cell lines were killed following exposure at 10(-8) M for 2 h; this concentration only reduced bone marrow colony formation to 83% (range, 50-100%) of control bone marrow. We then examined the pattern of bone marrow recovery after high dose melphalan (200 mg/m2) in patients with advanced breast cancer who were in remission following combination chemotherapy. To do this we compared the time of recovery of the blood count in three patients who received treated marrow and seven who received untreated marrow. Mean time to recovery of the peripheral white count (greater than 1.5 X 10(9)/liter) was 16.7 days (treated) and 18.3 days (untreated), respectively. Mean time to recovery of peripheral platelet count (greater than 50 X 10(9)/liter) was 23.7 days (treated) and 18.9 days (untreated), respectively. Patients continued in remission for 1-greater than 14 mo after high dose melphalan, and remission duration was similar in patients who received treated (6.2 mo) and untreated (7.3 mo) bone marrow. These findings indicate that treatment of bone marrow with LICR-LON-Fib75/abrin A-chain conjugate does not significantly impair bone marrow recovery, and it is, therefore, possible to rescue breast cancer patients with bone marrow that has been cleansed of infiltrating cancer cells. This may have an application in patients with poor-risk primary breast cancer who have micrometastases and who may benefit from intensive therapy, but it has minimal application in patients with more advanced disease.
我们设计了一种方法，利用单克隆抗体-毒素偶联物（LICR-LON-Fib75/相思子毒素A链）清除骨髓中的浸润性乳腺癌细胞，以便在高剂量治疗后挽救接受自体骨髓移植的患者。最初，我们在体外检测了这种偶联物的活性。七种人乳腺癌细胞系中有五种在10(-8)M浓度下暴露2小时后被杀死；该浓度仅使骨髓集落形成减少至对照骨髓的83%（范围为50-100%）。然后，我们检测了晚期乳腺癌患者在联合化疗缓解后接受高剂量美法仑（200mg/m2）治疗后骨髓恢复的模式。为此，我们比较了三名接受处理过的骨髓的患者和七名接受未处理骨髓的患者血细胞计数恢复的时间。外周白细胞计数恢复至大于1.5×10(9)/升的平均时间，接受处理的患者为16.7天，未接受处理的患者为18.3天。外周血小板计数恢复至大于50×10(9)/升的平均时间，接受处理的患者为23.7天，未接受处理的患者为18.9天。高剂量美法仑治疗后，患者持续缓解1-大于14个月，接受处理过的骨髓的患者（6.2个月）和接受未处理骨髓的患者（7.3个月）的缓解持续时间相似。这些发现表明，用LICR-LON-Fib75/相思子毒素A链偶联物处理骨髓不会显著损害骨髓恢复，因此，有可能用清除了浸润癌细胞的骨髓挽救乳腺癌患者。这可能适用于有微转移且可能从强化治疗中获益的高危原发性乳腺癌患者，但对病情更晚期的患者应用价值极小。
