Divgi C R, Scott A M, Gulec S, Broussard E K, Levy N, Young C, Capitelli P, Daghighian F, Williams J M, Finn R D
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Clin Cancer Res. 1995 Dec;1(12):1503-10.
An antimouse immune response is invariable following administration of murine monoclonal antibody (mAb), precluding effective multidose therapy. In advanced colorectal cancer patients, we carried out a pilot study with multiple doses of 131I-labeled CC49 administered with deoxyspergualin (DSG), an immunomodulator, to determine its effect on immune response. Cumulative toxicity and efficacy were also evaluated. Six patients with tumor-associated glycoprotein 72-expressing colorectal cancer were treated i.v. with 15 mCi/m2 131I-labeled to 20 mg mAb CC49 biweekly, along with concurrent DSG 200 mg/m2 daily for 5 days, for a maximum of four courses. None had received prior murine mAbs. All patients had targeting of radioactivity to known tumor sites following initial infusion. Four of six patients received all four courses of therapy, three without any acute side effects. In these patients, there was no change in serum clearance with variable tumor targeting following repeat infusions. Two patients had </= grade II anaphylactoid reactions, which were treated without sequelae. One of these had faster serum clearance of radioactivity following repeat infusions of 131I-labeled CC49. Human antimouse antibody titers in all patients were significantly less compared to concurrent times in patients receiving CC49 without DSG (P < 0.05). There was no correlation between the human antimouse antibody titer and serum clearance or tumor targeting of 131I-labeled CC49. There were no clinical responses. We concluded that multiple doses of murine antibody 131I-labeled CC49 can be safely administered with no change in serum or whole-body kinetics in 50% of patients treated biweekly. DSG may reduce the human immune response to the murine mAb.
给予鼠单克隆抗体（mAb）后，抗小鼠免疫反应不可避免，这使得多剂量有效治疗无法实现。在晚期结直肠癌患者中，我们开展了一项初步研究，给予多剂量的131I标记的CC49，并联合免疫调节剂脱氧精胍菌素（DSG），以确定其对免疫反应的影响。同时还评估了累积毒性和疗效。6例表达肿瘤相关糖蛋白72的结直肠癌患者接受静脉注射，每2周给予15 mCi/m2的131I标记的20 mg mAb CC49，同时每天给予200 mg/m2的DSG，持续5天，最多进行4个疗程。所有患者均未接受过鼠源性mAb治疗。首次输注后，所有患者的放射性均靶向已知肿瘤部位。6例患者中有4例接受了全部4个疗程的治疗，其中3例无任何急性副作用。在这些患者中，重复输注后血清清除率无变化，肿瘤靶向性各异。2例患者出现≤Ⅱ级类过敏反应，经治疗后无后遗症。其中1例患者在重复输注131I标记的CC49后放射性血清清除更快。与未使用DSG接受CC49治疗的患者同期相比，所有患者的人抗小鼠抗体滴度均显著降低（P<0.05）。人抗小鼠抗体滴度与131I标记的CC49的血清清除率或肿瘤靶向性之间无相关性。未观察到临床反应。我们得出结论，对于每2周接受治疗的50%的患者，多剂量的鼠源性抗体131I标记的CC49可以安全给药，血清或全身动力学无变化。DSG可能会降低人体对鼠源性mAb的免疫反应。
