CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 μg of antigen combined with 200 μg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic.

中文翻译：

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在同情使用计划中接受 VEGF 特异性主动免疫治疗程序治疗的癌症患者的特异性体液反应


CIGB-247 是一种癌症治疗疫苗，使用人血管内皮生长因子 (VEGF) 变体与细菌来源的佐剂 VSSP 混合作为抗原。 CIGB-247 已在两项 I 期临床试验（CENTAURO 和 CENTAURO-2）中进行了评估，表明在明确和受控的临床条件下选择的晚期癌症患者中具有安全性和免疫原性。幸存的患者每月接受重新免疫，其中一些显示出客观的临床益处。基于这些结果，针对不符合 CENTAURO 和 CENTAURO-2 临床试验严格进入标准，但可能从这种癌症治疗药物的应用中受益的患者启动了 CIGB-247 同情使用计划 (CUP)疫苗。通过 ELISA 在接种 400 μg 抗原和 200 μg VSSP 的患者血清样本中检测到 VEGF 特异性多克隆 IgM、IgA 和 IgG 抗体。多克隆抗体反应显示与其他 VEGF 家族成员分子（如 VEGF-C 和 VEGF-D）没有交叉反应性。来自免疫个体的血清能够阻断 VEGF 与其受体 VEGFR2 和 VEGFR1 的结合。从免疫血清中纯化的 IgG 部分具有上述特征，并且还抑制 VEGF 与治疗性重组抗体贝伐单抗（一种被批准用于治疗不同肿瘤的抗血管生成药物）之间的相互作用。 CIGB-247 CUP 参与者尚未记录到 CIGB-247 引起的严重不良事件。本文是我们关于接受 CIGB-247 CUP 癌症患者体液反应和安全特征研究结果的第一份报告。 该研究提供了独特的机会，不仅可以在更广泛的古巴癌症患者临床谱样本中测试 CIGB-247，而且可以在古巴医疗机构这些疾病的日常临床实践和治疗环境中进行测试。 CIGB-247 CUP 证明，在古巴多家医疗机构的日常临床实践条件下，对多种癌症患者的免疫和随访，复制了我们之前在临床试验中的发现：CIGB-247 是安全的且具有免疫原性。