ADC Development Services Targeting HGFR

As a promising and effective cancer therapy strategy, antibody-drug conjugates (ADCs) have been developed actively in recent years. Several approved ADCs have significant antitumor activity and a variety of investigated ADCs candidates also received positive preclinical and clinical therapy results, which further promote the advance of ADCs development.

Creative Biolabs’ scientific staff has extensive antibody development and drug synthesis experience, and now offers clients ADCs development services against all kinds of biomarkers such as HGFR. By using proprietary bio-conjugation technologies, we have demonstrated success in developing a large number of high-quality ADCs products.

Introduction of HGFR

Hepatocyte growth factor receptor (HGFR), also known as c-Met, is a tyrosine kinase receptor encoded by the MET gene. Mature HGFR contains two subunits, the alpha and beta subunit, linked through the disulfide linkage. Mature HGFR has tyrosine kinase activity. HGFR exists in the normal cells and involved in the migration, cell differentiation, construction of tubular three-dimensional structures, cell growth and angiogenesis via various signaling pathways, such as the PI3K, MAPK or Stat-Jak signaling pathways. Abnormal expression of HGFR can induce the occurring of cancer, which actives the formation of new angiogenesis to promote the tumor growth and spread. HGFR is limitedly expression in many human malignancies such as the kidney, liver, stomach, breast, and brain cancers. However, cancer cells have the ability to inhibit normal cells to express the HGFR, which is the cause of cancer persistence and spread to other tissues. Thus, HGFR is an attractive target in the targeted immunotherapy of cancer.

Representation of hepatocyte growth factor/c-Met canonical and non-canonical pathways in hepatocytes. Fig.1 Representation of hepatocyte growth factor/c-Met canonical and non-canonical pathways in hepatocytes. (García-Vilas, 2018)

Anti-HGFR ADC in Solid Tumors

Telisotuzumab vedotin (also known as ABBV‑399) is a novel ADC targeting HGFR. It consists of an anti-HGFR (c-Met) humanized monoclonal antibody ABT-700 conjugated to the cytotoxic monomethyl auristatin E (MMAE) via a valine-citrulline linker. Telisotuzumab vedotin has specific high-affinity to combine with the HGFR and directly carry MMAE to tumor cells, which can result in the mitosis and tumor cell death. Preclinical studies demonstrated that Telisotuzumab vedotin has powerful antitumor activity in c-Met-positive tumor cells. Besides, clinical trials showed that Telisotuzumab vedotin possesses potent antitumor activity in patients with MET-amplified advanced solid tumors. Furthermore, phase I trial also displayed the accepted safety and tolerability in patients with advanced solid tumors. Thus, it has been recommended to enter phase II study.

Mechanism of action of Telisotuzumab vedotin. Fig.2 Mechanism of action of Telisotuzumab vedotin.

What Can We Do for You?

At Creative Biolabs, we offer a full range of ADCs conjugation service with qualified antibodies and linker-payload. With excellent experience in specific antibodies development and bio-conjugation, we can help you to develop effective ADCs and we will work with you to validate each step of ADC development. Our one-stop ADCs services include ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation, ADC in vitro Analysis and ADC in vivo Analysis.

If you're requiring custom ADCs construction, please contact us for more information.

Reference

  1. García-Vilas, J. A.; Medina, M. Á. Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications. World journal of gastroenterology. 2018, 24(33): 3695.

For lab research use only, not for any in vivo human use.


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