Cancer Immunotherapy Laboratory, Department of Pharmaceuticals, and Animal Facility, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Playa Cubanacán, Havana 10600, Cuba.
Vaccine. 2012 Feb 27;30(10):1790-9. doi: 10.1016/j.vaccine.2012.01.006. Epub 2012 Jan 10.
CIGB-247 is a novel cancer therapeutic vaccine that uses a mutated form of human VEGF as antigen. Being metastatic disease the most dramatic factor of tumor biology affecting patient survival and cure, preclinical evaluation of the impact of CIGB-247 vaccination on experimental metastasis mouse models is highly relevant, and constitutes the focus of this work. CIGB-247 was administered in a weekly schedule known to effectively reduce primary tumor growth. The vaccine was tested in experimental and spontaneous metastasis models of colon (CT26), lung (3LL-D122) and breast (F3II) carcinomas growing in C57Bl/6 or BALB/c mice. Primary tumor growth parameters, metastatic counts, and/or animal survival were recorded. Histology and specific humoral and cellular responses to the vaccine were evaluated. As compared to control groups, CIGB-247 vaccination significantly reduced the number and size of metastatic tumor foci in lungs after intravenous inoculation of CT26 and 3LL-D122 tumor cells. Spontaneous lung dissemination from 3LL-D122 and F3II breast tumor cells implanted in the footpad, or subcutaneously, was also reduced by immunization with CIGB-247. The vaccine elicited in both mouse strains antibodies specific for human and murine VEGF that effectively blocked the interaction of VEGF with VEGF receptor 2. Differing from other experimental reports that describe the use of VEGF for active tumor immunotherapy, CIGB-247 elicited a specific cellular response, measured both by a DTH increment and the induction of spleen cells cytotoxic to syngeneic tumor cells producing murine VEGF. In summary our results reinforce the potential of CIGB-247 vaccination to reduce both tumor growth and the number and size of tumor metastasis in lungs, the latter both after direct inoculations of cells in the blood stream, or as part of primary tumor progression in immunocompetent mice.
CIGB-247 是一种新型癌症治疗疫苗，使用突变形式的人 VEGF 作为抗原。作为转移性疾病，是影响患者生存和治愈的最显著肿瘤生物学因素，因此，对 CIGB-247 疫苗接种对实验性转移小鼠模型的影响进行临床前评估非常重要，这也是这项工作的重点。CIGB-247 按已知能有效减少原发性肿瘤生长的每周方案进行给药。该疫苗在 C57Bl/6 或 BALB/c 小鼠中生长的结肠（CT26）、肺（3LL-D122）和乳腺（F3II）癌的实验性和自发性转移模型中进行了测试。记录原发性肿瘤生长参数、转移性计数和/或动物存活率。评估了组织学以及对疫苗的特异性体液和细胞反应。与对照组相比，CIGB-247 疫苗接种显著减少了静脉接种 CT26 和 3LL-D122 肿瘤细胞后肺部转移瘤灶的数量和大小。通过用 CIGB-247 免疫接种，也减少了 3LL-D122 和 F3II 乳腺肿瘤细胞从足底或皮下植入后自发肺转移。该疫苗在两种小鼠品系中均引起针对人源和鼠源 VEGF 的特异性抗体，有效地阻断了 VEGF 与 VEGF 受体 2 的相互作用。与其他描述使用 VEGF 进行主动肿瘤免疫治疗的实验报告不同，CIGB-247 引起了特异性的细胞反应，这通过 DTH 增加和诱导产生鼠源 VEGF 的同源肿瘤细胞的脾细胞细胞毒性来衡量。总之，我们的结果加强了 CIGB-247 疫苗接种减少肺部肿瘤生长和转移瘤数量和大小的潜力，无论是直接接种血液中的细胞，还是作为免疫功能正常小鼠中原发性肿瘤进展的一部分。
