Search results for "Bispecific antibody"

Preliminary results from a phase I study of GBR 1302, a bispecific antibody T-cell engager, in HER2 positive cancers

2018

A phase I study of the bispecific antibody T-cell engager GBR 1302 in subjects with HER2-positive cancers.

2017

TPS3091 Background: GBR 1302, a bispecific antibody based on Glenmark’s BEAT platform, is designed to recruit cytotoxic T-cells (independent of their specificity) to HER2-positive cancer cells where they are activated by the CD3e-specific domain of the molecule. Preclinically, GBR 1302 has demonstrated potent killing of HER2-positive human cancer cells (HER2 3+ or 2+ by IHC HercepTest), as well as growth suppression of the trastuzumab-resistant cell line JIMT-1. In contrast, the GBR 1302 concentration required to kill primary cardiomyocytes with normal HER2 levels was up to 1000 times greater than the concentration needed to kill HER2 3+ tumor cell lines. This study will determine safety a…

Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.

2016

The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.

Preliminary biomarker and pharmacodynamic data from a phase I study of single-agent bispecific antibody T-cell engager GBR 1302 in subjects with HER2…

2018

69 Background: HER2 is overexpressed in many solid tumors and is a validated therapeutic target. GBR 1302 is a HER2xCD3 bispecific antibody engineered (using Glenmark’s BEAT® platform) to direct T-cells to HER2-expressing tumor cells. GBR1302-101 (NCT02829372) is an ongoing, multicenter, open-label, first-in-human study of GBR 1302 in subjects with HER2-positive cancers to evaluate the safety, tolerability, and preliminary efficacy of GBR 1302, and to elucidate the mechanism(s) by which it redirects T-cells to tumor and enhances cytolytic activity of cytotoxic T-cells. Methods: Adults with progressive HER2-positive solid tumors with no available standard or curative treatment receive intra…

Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the onc…

2015

abstract The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype. 6PHU3 exerts potent killing of cancer cells in vitro with EC50 values in the pg/mL range. Subcutaneous xenograft tumors in NSG mice engrafted with human PBMCs are eradicat…

A phase I, open-label, dose-escalation trial of BI 764532, a DLL3/CD3 bispecific antibody, in patients (pts) with small cell lung carcinoma (SCLC) or…

2021

TPS8588 Background: First-line standard of care for pts with metastatic SCLC and neuroendocrine carcinoma (NEC) is platinum-based chemotherapy ± immunotherapy. While the addition of anti-PD1 antibodies has improved outcomes, nearly all pts relapse and prognosis is poor. There is a major unmet need for additional treatment (tx) options. BI 764532 is a delta-like ligand 3 (DLL3)/CD3 T cell engaging bispecific antibody. DLL3 is expressed on the cell surface of many SCLC and NEC tumors, but not on normal cells. In preclinical studies, BI 764532 induced cytotoxicity of DLL3-positive cells and showed anti-tumor activity in animal models. Methods: NCT04429087 is a first-in-human, open-label, dose…

The inhibitors - a challenge for the management of patients with hereditary haemophilia A.

2018

Abstract Introduction. Our research strategy was aimed at evaluating the possible implication of the type of factor VIII product administered as substitution treatment to haemophilia A patients in the occurrence of inhibitors and their consequences on the management. Methods. Scientific articles from July 2015 to July 2017 were searched using the PubMed and PubMed Central databases. The used search terms included “haemophilia A”, “inhibitors”, “plasma-derived factor VIII” and “recombinant factor VIII”. Results. The risk factors for inhibitors occurrence may be patients-related (genetic and nongenetic) and treatment-related. The possibility of a correlation between the increased purity of fa…