ADI-PEG20 联合FOLFOX 治疗晚期胃肠道恶性肿瘤以肝细胞癌受试者为主的 第1-2期临床研究
主要目标是由设盲独立中心评估(BICR)按照RECIST 1.1标准评估确定客观缓解率(ORR),次要目标是确定无进展生存期(PFS),总生存期(OS),缓解持续时间(DoR),疾病控制率(DCR),药效学,药代动力学,免疫原性及AFP变化。
在对既往系统治疗失败的晚期肝细胞癌受试者中进行的ADI-PEG 20+BSC vs.安慰剂+BSC的随机、双盲、多中心的Ⅲ期研究
本试验是针对既往系统治疗失败的晚期肝细胞癌受试者,验证ADI-PEG20治疗的有效性和安全性。
在对既往系统治疗失败的晚期肝细胞癌受试者中进行的ADI-PEG 20+BSC vs.安慰剂+BSC的随机、双盲、多中心的Ⅲ期研究
本试验是针对既往系统治疗失败的晚期肝细胞癌受试者,验证ADI-PEG20治疗的有效性和安全性。
100 项与 Designerx Pharmaceuticals, Inc. 相关的临床结果
0 项与 Designerx Pharmaceuticals, Inc. 相关的专利(医药)
PEGylated arginine deiminase can modulate tumor immune microenvironment by affecting immune checkpoint expression, decreasing regulatory T cell accumulation and inducing tumor T cell infiltration
Article
作者: He, Yudou ; He, Wei ; Lu, Hsin-Tze ; Dai, Zhaoming ; Brin, Elena ; Wu, Katherine
PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers in vitro and in vivo - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment. ADI-PEG 20 induced immunosuppressive programmed death-ligand 1 expression on some cancer cells in vitro, but the magnitude of the increase was cell line dependent and in most relatively small. Using healthy donor human peripheral blood mononuclear cells (PBMCs) we discovered that when present during initiation of T cell activation (but not later on) ADI-PEG 20 can inhibit their differentiation after early activation stage manifested by the expression of CD69 marker. In vivo, ADI-PEG 20 induced tumor T-cell infiltration in a poorly immunogenic syngeneic mouse melanoma B16-F10 model and reduced its growth as a single agent or when combined with anti-PD-1 mAb. It was also effective by itself or in combination with anti-PD-L1 mAb in CT26 colon carcinoma syngeneic model.
100 项与 Designerx Pharmaceuticals, Inc. 相关的药物交易
100 项与 Designerx Pharmaceuticals, Inc. 相关的转化医学