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INHIBITION OF TUMOR ANGIOGENESIS BY CHECKPOINT INHIBITORS AND ACTIVE VACCINATION

机译:检查点抑制剂和主动接种疫苗对肿瘤血管生成的抑制作用

摘要

Disclosed are compositions of matter, methods, and protocols useful for treatment of cancer through induction of anti-angiogenic immune responses by vaccination together with immune modulation triggered by checkpoint inhibitors. The invention provides placenta, placental endothelial, placental fibroblasts, and mixtures thereof as immunogens, whose anti-angiogenic activity is augmented by utilization of checkpoint inhibitors. Means of differentiating tumor cells directly into endothelial or endothelial-like cells and utilizing said cells as immunogens for the purpose of inducing immunity against blood vessels feeding tumors. In one embodiment CTLA4 blockade is performed in combination with an immunogen capable of triggering immunity towards tumor endothelial cells. In another embodiment blockade of the PD1-PD1 ligand pathway is performed in combination with induction of anti-angiogenic immune response.
机译:公开了通过疫苗接种诱导抗血管生成免疫应答以及由检查点抑制剂触发的免疫调节,可用于治疗癌症的物质,方法和方案的组成。本发明提供了胎盘,胎盘内皮,胎盘成纤维细胞及其混合物作为免疫原,其抗血管生成活性通过利用检查点抑制剂得到增强。将肿瘤细胞直接分化为内皮细胞或内皮样细胞并利用所述细胞作为免疫原的方法,目的是诱导针对饲喂肿瘤的血管的免疫力。在一个实施方案中,CTLA4阻断与能够触发针对肿瘤内皮细胞的免疫力的免疫原结合进行。在另一个实施方案中,与抗血管生成免疫应答的诱导相结合进行PD1-PD1配体途径的阻断。

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