Braly Patricia, Nicodemus Christopher F, Chu Christina, Collins Yvonne, Edwards Robert, Gordon Alan, McGuire William, Schoonmaker Christopher, Whiteside Theresa, Smith Lesley Mary, Method Michael
Hematology and Oncology Specialists, 39 Starbrush Circle, Covington, LA 70433, USA.
J Immunother. 2009 Jan;32(1):54-65. doi: 10.1097/CJI.0b013e31818b3dad.
Oregovomab is a monoclonal antibody that recognizes CA125 and forms circulating immune complexes that can elicit immunity against both tumor antigen and tumor. This study was designed to assess combining this immunotherapy at 2 dosing schedules with front-line chemotherapy in patients with advanced ovarian cancer. Forty patients with stage III/IV carcinomas were randomized to receive a 2 mg oregovomab infusion either the same day [simultaneous infusion (SIM)] or 1 week after [1-week delayed (OWD)] standard carboplatin-paclitaxel chemotherapy at cycles 1, 3, and 5, then quarterly for up to 11 antibody doses. The primary end point was antibody response to oregovomab. Secondary end points included cellular immune response, response rate to front-line treatment, and progression-free survival. A different immune response pattern was observed between the SIM arm and the OWD arm, baseline plasma cytokines were balanced. Humoral immunity occurred more rapidly (P=0.0033) and with greater magnitude in the SIM arm. Absolute lymphocyte counts decreased in the SIM arm at cycles 3 and 5 compared with baseline. Treatment emergent CA125-specific cellular immunity was measured more commonly with SIM (P=0.04) and clinical parameters directionally favored this schedule. The immune responses were stronger than those measured in a previous maintenance monoimmunotherapy protocol. Immunotherapy-associated toxicity was minimal in this study. Front-line chemotherapy with carboplatin-paclitaxel has immune adjuvant properties when combined with oregovomab immunotherapy; however, schedule is important. SIM strategies of carboplatin and paclitaxel should be further studied with oregovomab and other antigen-specific cancer immunotherapy approaches.
奥瑞珠单抗是一种单克隆抗体，可识别CA125并形成循环免疫复合物，从而引发针对肿瘤抗原和肿瘤的免疫反应。本研究旨在评估在晚期卵巢癌患者中，将这种免疫疗法以两种给药方案与一线化疗联合使用的效果。40例III/IV期癌患者被随机分组，在第1、3和5周期接受标准卡铂-紫杉醇化疗的同一天[同步输注（SIM）]或之后1周[延迟1周（OWD）]输注2mg奥瑞珠单抗，然后每季度一次，最多输注11剂抗体。主要终点是对奥瑞珠单抗的抗体反应。次要终点包括细胞免疫反应、一线治疗的反应率和无进展生存期。在SIM组和OWD组之间观察到不同的免疫反应模式，基线血浆细胞因子是平衡的。体液免疫在SIM组中发生得更快（P=0.0033）且程度更大。与基线相比，SIM组在第3和5周期时绝对淋巴细胞计数下降。与OWD组相比，SIM组更常检测到治疗引起的CA125特异性细胞免疫（P=0.04），并且临床参数在趋势上有利于该给药方案。免疫反应比之前的维持单免疫疗法方案中测得的更强。在本研究中，免疫疗法相关的毒性最小。卡铂-紫杉醇一线化疗与奥瑞珠单抗免疫疗法联合使用时具有免疫佐剂特性；然而，给药方案很重要。卡铂和紫杉醇的SIM策略应与奥瑞珠单抗和其他抗原特异性癌症免疫疗法进一步研究。
