Renner C, Hartmann F, Pfreundschuh M
Medical Department I, Saarland University, Homburg, Germany.
Cancer Immunol Immunother. 1997 Nov-Dec;45(3-4):184-6. doi: 10.1007/s002620050428.
A group of 15 patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural-killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's associated CD30 antigen. The antibody was given four times every 3-4 days, starting with 1 mg/m2. The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2. Side-effects were rare and consisted of fever, pain in involved lymph nodes and a maculopapulous rash. Nine patients developed human anti-(mouse immunoglobulin) antibodies. One complete and one partial remission (lasting 5 and 3 months, respectively), three minor responses (1 to 11+ months), and one mixed response were achieved. There was no clear-cut dose side-effect or dose/response correlation. NK cell activity increased in most of the patients treated with 4 mg/m2 or higher doses but lasted no longer than 6 weeks after therapy. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the antibody to allow retreatment of responding patients.
一组15例难治性霍奇金病患者在I/II期试验中接受了自然杀伤（NK）细胞激活双特异性单克隆抗体HRS-3/A9治疗，该抗体针对Fcγ受体III（CD16抗原）和霍奇金相关的CD30抗原。抗体每3 - 4天给药4次，起始剂量为1mg/m²。治疗耐受性良好，在64mg/m²时未达到最大耐受剂量。副作用罕见，包括发热、受累淋巴结疼痛和斑丘疹。9例患者产生了人抗（鼠免疫球蛋白）抗体。获得了1例完全缓解和1例部分缓解（分别持续5个月和3个月）、3例轻微反应（持续1至11 +个月）以及1例混合反应。没有明确的剂量 - 副作用或剂量/反应相关性。大多数接受4mg/m²或更高剂量治疗的患者NK细胞活性增加，但治疗后持续不超过6周。我们的结果鼓励采用这种新型免疫治疗方法进行进一步的临床试验，并强调有必要降低抗体的免疫原性，以便对有反应的患者进行再次治疗。
