Morera Yanelys, Sánchez Javier, Bequet-Romero Mónica, Selman-Housein Katty-Hind, de la Torre Ana, Hernández-Bernal Francisco, Martín Yenima, Garabito Acralys, Piñero Jesús, Bermúdez Cimara, de la Torre Josué, Ayala Marta, Gavilondo Jorge V
Center for Genetic Engineering and Biotechnology, 31 Ave. between 158 and 190 Streets, Cubanacán, Playa, Havana, Cuba.
Center for Genetic Engineering and Biotechnology, 31 Ave. between 158 and 190 Streets, Cubanacán, Playa, Havana, Cuba.
Vaccine. 2017 Jun 16;35(28):3582-3590. doi: 10.1016/j.vaccine.2017.05.020. Epub 2017 May 20.
CIGB-247 is a cancer therapeutic vaccine, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the adjuvant VSSP, a bacterially-derived adjuvant. The vaccine have demonstrated efficacy in several murine malignancy models. These studies supported the rationale for a phase I clinical trial where safety, tolerance, and immunogenicity of CIGB-247 was studied in patients with advanced solid tumors at three antigen dose level. Surviving individuals of this clinical trial were eligible to receive off-trial voluntary re-immunizations. The present work is focus in the immunological follow up of these patients after approximately three years of immunizations, without additional oncological treatments. Long term vaccination was feasible and safe. Our results indicated that after sustained vaccination most of the patients conserved their seroconversion status. The specific anti-VEGF IgG titer diminished, but in all the cases keeps values up from the pre-vaccination levels. Continued vaccination was also important to produce a gradual shift in the anti-VEGF IgG response from IgG1 to Ig4. Outstanding, our results indicated that long-term off-trial vaccination could be associated with the maintaining of one reserve of antibodies able to interfere with the VEGF/Receptor interaction and the production of IFNγ secretion in CD8 cells. The results derived from the study of this series of patients suggest that long term therapeutic vaccination is a feasible strategy, and highlight the importance of continuing the clinical development program of this novel cancer therapeutic vaccine candidate. We also highlight the future clinical applications of CIGB-247 in cancer and explain knowledge gaps that future studies may address. Registration number and name of trial registry: RPCEC00000102. Cuban Public Clinical Trial Registry (WHO accepted Primary Registry). Available from: http://registroclinico.sld.cu/.
CIGB-247是一种癌症治疗性疫苗，它以重组修饰的人血管内皮生长因子（VEGF）作为抗原，并与细菌衍生佐剂VSSP联合使用。该疫苗已在多种小鼠恶性肿瘤模型中显示出疗效。这些研究为一项I期临床试验提供了依据，该试验在三个抗原剂量水平上对晚期实体瘤患者进行了CIGB-247的安全性、耐受性和免疫原性研究。该临床试验的幸存者有资格接受试验外的自愿再免疫。目前的工作重点是在这些患者接种疫苗约三年后，在没有额外肿瘤治疗的情况下对其进行免疫学随访。长期接种疫苗是可行且安全的。我们的结果表明，持续接种疫苗后，大多数患者保持了血清转化状态。特异性抗VEGF IgG滴度有所下降，但在所有情况下均保持高于接种前水平的值。持续接种疫苗对于使抗VEGF IgG反应从IgG1逐渐转变为Ig4也很重要。值得注意的是，我们的结果表明，长期的试验外接种疫苗可能与维持一组能够干扰VEGF/受体相互作用并产生CD8细胞中IFNγ分泌的抗体储备有关。对这一系列患者的研究结果表明，长期治疗性疫苗接种是一种可行的策略，并突出了继续推进这种新型癌症治疗候选疫苗临床开发计划的重要性。我们还强调了CIGB-247在癌症方面的未来临床应用，并解释了未来研究可能解决的知识空白。试验注册号及试验注册名称：RPCEC00000102。古巴公共临床试验注册库（世界卫生组织认可的一级注册库）。可从：http://registroclinico.sld.cu/获取。
