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SHR-1210 in Combination With BP102 and XELOX in Patient With Metastatic Colorectal Cancer

ABSTRACT: This is an open label, single-arm, multi-center, phase II study of SHR-1210 in metastatic colorectal cancer patients with the recurrent lesion(s) post-surgery or the untreated mCRC. SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1).BP102 is a humanized recombinant monoclonal IgG1 antibody. The primary objective of this study is to investigate the safety and efficacy of the subjects who given the combination therapy.

DISEASE(S): Metastatic Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2282196 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Transcriptomic analysis of advanced solid tumors in first-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody [3'SAGE-seq]

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Project description:Hydrogen peroxide (H2O2) is a potent signaling molecule influencing various aspects of plant growth and development. Its limited lifetime and specific production sites in the plant cell necessitate the existence of specialized mechanisms that relay H2O2-encoded information. To discover such mechanisms, we focused on peroxisomal H2O2 production triggered by enhanced photorespiration in Arabidopsis mutants lacking catalase activity (cat2-2), and looked for second-site mutations that attenuate the negative effects (Fv'/Fm' decline and lesion formation) of H2O2 build up. A mutation residing in the GRAS family transcriptional regulator SHORT-ROOT (SHR) was found to underlie the increased performance of cat2-2 knock-outs under photorespiratory stress. In contrast to shr, introduction of the scr mutation in cat2-2 background did not improve the photorespiratory performance of plants lacking peroxisomal catalase. The absence of SHR negatively affected the activity of the photorespiratory enzymes glycolate oxidase and catalase, which was accompanied with elevated glycolate content and inability to accumulate glycine under conditions promoting photorespiration. The transcriptome signature of cat2-2 shr-6 double mutants exposed to photorespiratory stress lacked jasmonate-dependent signaling components, otherwise induced in cat2-2. The photorespiratory phenotype of cat2-2 was found to be modulated by exogenous sugars both in the presence and absence of shr. Taken together, these findings highlight a crucial role for SHR in H2O2 signal transduction and stress tolerance.

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