Morton B A, Beatty B G, Mison A P, Wanek P M, Beatty J D
Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, California 91010.
Cancer Res. 1990 Feb 1;50(3 Suppl):1008s-1010s.
The efficacy of bone marrow transplantation (BMT) for the prevention of 90Y toxicity and extension of survival in nude mice with i.p. LS174T carcinomatosis was evaluated. 90Y-labeled monoclonal antibody (MAB) directed against carcinoembryonic antigen (90Y-anti-CEA MAB) at a dose of 120 microCi caused no deaths due to treatment toxicity and increased the duration of animal survival. No long term cures were obtained in these mice. At doses of 160 microCi or more 90Y-anti-CEA MAB led to hematological deaths. Nude mice were given i.p. injections of 10(6) LS174T tumor cells on day 0. On day 7 the mice received 90Y-anti-CEA MAB i.p. at doses of 120-225 microCi. Syngeneic bone marrow cells (10(7) cells) were then injected i.v. into the mice at 1, 3, 5, 7, 10, or 14 days following 90Y treatment. In the absence of BMT, toxic deaths for animals given 175 microCi 90Y were 11 of 24 (46%) with a median survival of 17 days and 13 of 20 (65%) for animals given 225 microCi 90Y with a median survival of 14 days. Animals receiving the same two doses of 90Y and given BMT 5 days following the 90Y treatment showed 0 of 24 (0%) and 0 of 54 (0%) toxicity deaths, respectively. The optimal time of BMT in relation to 90Y therapy was dependent upon the dose of 90Y-anti-CEA MAB (225 microCi, 3-5 days; 175 microCi, 5-14 days). The mean survival in tumor bearing animals was extended from 31.7 +/- 1.2 (SE) to 45.3 +/- 2.0 days by treatment with 120 microCi of 90Y-anti-CEA MAB. By increasing the dose of 90Y-anti-CEA MAB to 225 microCi and undertaking BMT 5 days later the mean survival was further extended to 63.2 +/- 3.6 days (P less than 0.005). BMT administered at the optimal times can prevent toxic deaths and facilitates higher, more effective doses of tumor specific 90Y-MAB.
评估了骨髓移植（BMT）预防腹腔注射LS174T癌病裸鼠90Y毒性及延长生存期的效果。剂量为120微居里的90Y标记抗癌胚抗原单克隆抗体（90Y-抗CEA MAB）未因治疗毒性导致死亡，且延长了动物生存期。这些小鼠未获得长期治愈。剂量为160微居里或更高时，90Y-抗CEA MAB导致血液学死亡。在第0天给裸鼠腹腔注射10⁶个LS174T肿瘤细胞。在第7天，小鼠腹腔注射剂量为120 - 225微居里的90Y-抗CEA MAB。然后在90Y治疗后的第1、3、5、7、10或14天给小鼠静脉注射同基因骨髓细胞（10⁷个细胞）。在未进行BMT的情况下，接受175微居里90Y的动物中24只中有11只（46%）因毒性死亡，中位生存期为17天；接受225微居里90Y的20只中有13只（65%）因毒性死亡，中位生存期为14天。接受相同两剂量90Y且在90Y治疗后5天进行BMT的动物，毒性死亡分别为24只中的0只（0%）和54只中的0只（0%）。BMT相对于90Y治疗的最佳时间取决于90Y-抗CEA MAB的剂量（225微居里，3 - 5天；175微居里，5 - 14天）。用120微居里的90Y-抗CEA MAB治疗使荷瘤动物的平均生存期从31.7±1.2（SE）天延长至45.3±2.0天。将90Y-抗CEA MAB剂量增加到225微居里并在5天后进行BMT，平均生存期进一步延长至63.2±3.6天（P＜0.005）。在最佳时间进行BMT可预防毒性死亡，并有助于使用更高、更有效的肿瘤特异性90Y-MAB剂量。
