Delving into the Latest Updates on Concortis Biosystems Corp. with Synapse

Overview

Tags

Neoplasms

Immune System Diseases

Respiratory Diseases

Antibody drug conjugate (ADC)

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	2
Hemic and Lymphatic Diseases	1
Infectious Diseases	1
Immune System Diseases	1

Top 5 Drug Type	Count

Antibody drug conjugate (ADC)	2

Top 5 Target	Count

c-Met(Hepatocyte growth factor receptor)	1
CD38(Lymphocyte differentiation antigen CD38)	1

AbstractAntibody–drug conjugates (ADC) are designed to be stable in circulation and to release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, and degradation in tumor cells. Efficient internalization and routing to lysosomes where proteolysis can take place is therefore essential. For many cell surface proteins and carbohydrate structures on tumor cells, however, the magnitude of these processes is insufficient to allow for an effective ADC approach. We hypothesized that we could overcome this limitation by enhancing lysosomal ADC delivery via a bispecific antibody (bsAb) approach, in which one binding domain would provide tumor specificity, whereas the other binding domain would facilitate targeting to the lysosomal compartment. We therefore designed a bsAb in which one binding arm specifically targeted CD63, a protein that is described to shuttle between the plasma membrane and intracellular compartments, and combined it in a bsAb with a HER2 binding arm, which was selected as model antigen for tumor-specific binding. The resulting bsHER2xCD63his demonstrated strong binding, internalization and lysosomal accumulation in HER2-positive tumor cells, and minimal internalization into HER2-negative cells. By conjugating bsHER2xCD63his to the microtubule-disrupting agent duostatin-3, we were able to demonstrate potent cytotoxicity of bsHER2xCD63his-ADC against HER2-positive tumors, which was not observed with monovalent HER2- and CD63-specific ADCs. Our data demonstrate, for the first time, that intracellular trafficking of ADCs can be improved using a bsAb approach that targets the lysosomal membrane protein CD63 and provide a rationale for the development of novel bsADCs that combine tumor-specific targeting with targeting of rapidly internalizing antigens. Mol Cancer Ther; 15(11); 2688–97. ©2016 AACR.

01 May 2015·Molecular Cancer TherapeuticsQ2 · MEDICINE

High Turnover of Tissue Factor Enables Efficient Intracellular Delivery of Antibody–Drug Conjugates

Q2 · MEDICINE

Article

Author: Zhu, Tong ; Satijn, David ; de Goeij, Bart E.C.G. ; Wubbolts, Richard ; van Berkel, Patrick H.C. ; Miao, David ; Freitag, Claudia M. ; Chen, Gary ; Khasanov, Alisher ; Parren, Paul W.H.I. ; Bleeker, Wim K.

AbstractAntibody–drug conjugates (ADC) are emerging as powerful cancer treatments that combine antibody-mediated tumor targeting with the potent cytotoxic activity of toxins. We recently reported the development of a novel ADC that delivers the cytotoxic payload monomethyl auristatin E (MMAE) to tumor cells expressing tissue factor (TF). By carefully selecting a TF-specific antibody that interferes with TF:FVIIa-dependent intracellular signaling, but not with the procoagulant activity of TF, an ADC was developed (TF-011-MMAE/HuMax-TF-ADC) that efficiently kills tumor cells, with an acceptable toxicology profile. To gain more insight in the efficacy of TF-directed ADC treatment, we compared the internalization characteristics and intracellular routing of TF with the EGFR and HER2. Both in absence and presence of antibody, TF demonstrated more efficient internalization, lysosomal targeting, and degradation than EGFR and HER2. By conjugating TF, EGFR, and HER2-specific antibodies with duostatin-3, a toxin that induces potent cytotoxicity upon antibody-mediated internalization but lacks the ability to induce bystander killing, we were able to compare cytotoxicity of ADCs with different tumor specificities. TF-ADC demonstrated effective killing against tumor cell lines with variable levels of target expression. In xenograft models, TF-ADC was relatively potent in reducing tumor growth compared with EGFR- and HER2-ADCs. We hypothesize that the constant turnover of TF on tumor cells makes this protein specifically suitable for an ADC approach. Mol Cancer Ther; 14(5); 1130–40. ©2015 AACR.

100 Deals associated with Concortis Biosystems Corp.

Login to view more data

100 Translational Medicine associated with Concortis Biosystems Corp.

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 20 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

2

Login to view more data