Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer
Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer
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DOI：
10.1200/jco.2005.05.5335
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发表时间：
2006-10-10
影响因子：
45.3
通讯作者：
Fakhrai, Habib
中科院分区：
文献类型：
--
作者：
Nemunaitis, John;Dillman, Robert O.;Fakhrai, Habib
PurposeBelagenpumatucel-L是一种非病毒基因为基础的同种异体肿瘤细胞疫苗，证明增强肿瘤抗原识别作为结果的转化生长因子β-2 inhibit 1 n.Patients and MethodsWe进行了一项随机，剂量可变，II期临床试验，涉及阶段II，IIIA，IIIB和IV非小细胞肺癌患者。每例患者接受三种剂量（1.25、2.5或5.0 × 10（7）个细胞/注射）中的一种，每月或每隔一个月注射一次，最多注射16次。免疫功能，安全性和抗癌活性monitored.ResultsSeventy-five患者（2阶段II，12阶段IIIA，15阶段IIIB，和46阶段IV患者）共接受了550次疫苗接种。未观察到显著不良事件。在接受>= 2.5 × 10（7）个细胞/注射的患者中证实了剂量相关的生存差异（P =.0069）。重点关注61例晚期（IIIB和IV）可评估患者，达到了15%的部分缓解率。高剂量组合并后1年和2年的估计生存概率分别为68%和52%，低剂量组分别为39%和20%。在61例晚期（IIIB和IV）患者中探索了免疫功能。在临床应答者（干扰素γ，P = 0.006;白细胞介素[IL]-6，P = 0.004; IL-4，P = 0.007）中观察到细胞因子产生增加（与疾病进展患者相比，第12周），这些患者对疫苗HLA的抗体介导的应答也升高（P = 0.014）。此外，阳性酶联免疫斑点反应belagenpumatucel-L表现出相关趋势（P = 0.086）与临床反应的患者实现稳定的疾病或更好的。
PurposeBelagenpumatucel-L is a nonviral gene-based allogeneic tumor cell vaccine that demonstrates enhancement of tumor antigen recognition as a result of transforming growth factor beta-2 inhibition.Patients and MethodsWe performed a randomized, dose-variable, phase II trial involving stages II, IIIA, IIIB, and IV non-small-cell lung cancer patients. Each patient received one of three doses (1.25, 2.5, or 5.0 x 10(7) cells/injection) of belagenpumatucel-L on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety, and anticancer activity were monitored.ResultsSeventy-five patients ( two stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients) received a total of 550 vaccinations. No significant adverse events were observed. A dose-related survival difference was demonstrated in patients who received >= 2.5 x 10(7) cells/injection ( P =.0069). Focusing on the 61 late-stage ( IIIB and IV) assessable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% and 52%, respectively for the higher dose groups combined and 39% and 20%, respectively, for the low-dose group. Immune function was explored in the 61 advanced-stage ( IIIB and IV) patients. Increased cytokine production ( at week 12 compared with patients with progressive disease) was observed among clinical responders ( interferon gamma, P =.006; interleukin [IL] - 6, P =.004; IL-4, P =.007), who also displayed an elevated antibody-mediated response to vaccine HLAs ( P =.014). Furthermore, positive enzyme-linked immunospot reactions to belagenpumatucel-L showed a correlation trend ( P =.086) with clinical responsiveness in patients achieving stable disease or better.ConclusionBelagenpumatucel-L is well tolerated, and the survival advantage justifies further phase III evaluation.