Wagner Samuel C, Ichim Thomas E, Ma Hong, Szymanski Julia, Perez Jesus A, Lopez Javier, Bogin Vladimir, Patel Amit N, Marincola Francisco M, Kesari Santosh
Batu Biologics Inc., Towne Center Drive, San Diego, CA, 92121, USA.
Pan Am Cancer Treatment Center, Tijuana, Mexico.
J Transl Med. 2015 Oct 29;13:340. doi: 10.1186/s12967-015-0688-5.
Angiogenesis is essential for the growth and metastasis of solid tumors. The tumor endothelium exists in a state of chronic activation and proliferation, fueled by the tumor milieu where angiogenic mediators are aberrantly over-expressed. Uncontrolled tumor growth, immune evasion, and therapeutic resistance are all driven by the dysregulated and constitutive angiogenesis occurring in the vasculature. Accordingly, great efforts have been dedicated toward identifying molecular signatures of this pathological angiogenesis in order to devise selective tumor endothelium targeting therapies while minimizing potential autoimmunity against physiologically normal endothelium. Vaccination with angiogenic antigens to generate cellular and/or humoral immunity against the tumor endothelium has proven to be a promising strategy for inhibiting or normalizing tumor angiogenesis and reducing cancer growth. Here we review tumor endothelium vaccines developed to date including active immunization strategies using specific tumor endothelium-associated antigens and whole endothelial cell-based vaccines designed to elicit immune responses against diverse target antigens. Among the novel therapeutic options, we describe a placenta-derived endothelial cell vaccine, ValloVax™, a polyvalent vaccine that is antigenically similar to proliferating tumor endothelium and is supported by pre-clinical studies to be safe and efficacious against several tumor types.
血管生成对于实体瘤的生长和转移至关重要。肿瘤内皮处于慢性激活和增殖状态，由肿瘤微环境驱动，其中血管生成介质异常过度表达。不受控制的肿瘤生长、免疫逃逸和治疗抗性均由血管系统中发生的失调性和持续性血管生成所驱动。因此，人们致力于识别这种病理性血管生成的分子特征，以便设计选择性靶向肿瘤内皮的疗法，同时将针对生理正常内皮的潜在自身免疫降至最低。用血管生成抗原进行疫苗接种以产生针对肿瘤内皮的细胞和/或体液免疫，已被证明是抑制或使肿瘤血管生成正常化并减少癌症生长的一种有前景的策略。在此，我们综述了迄今为止开发的肿瘤内皮疫苗，包括使用特定肿瘤内皮相关抗原的主动免疫策略以及旨在引发针对多种靶抗原的免疫反应的全内皮细胞疫苗。在这些新型治疗选择中，我们描述了一种胎盘来源的内皮细胞疫苗ValloVax™，这是一种多价疫苗，在抗原性上与增殖的肿瘤内皮相似，临床前研究表明其对多种肿瘤类型安全有效。
