Development of Biparatopic EGFR-targeted Bispecific ADCs

Bispecific antibodies have emerged as promising agents for therapeutic use that act by simultaneously binding two separate antigens or different epitopes of the same antigen. Antibody-drug conjugates (ADCs) are also considered a new and promising therapeutic method that combines the target specificity of an antibody with the high potency of a synthetic small molecule. Based on the effective cancer therapy outcome of bispecific antibody and ADC, bispecific ADC appears as a novel format that combines the advantages of bispecific antibody and ADC.

Creative Biolabs has over ten years of practical antibody production and custom bio-conjugation experience for the best ADCs construction. Our high-quality ADC development services include ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation, ADC in vitro Analysis, and ADC in vivo Analysis. Now we provide a full set of services to help clients develop bispecific biparatopic antibody-drug conjugates against EGFR. With a diverse range of modifications available for linkers or linker-payloads, we will routinely meet our clients' specifications with unusual, custom made products.

Introduction of EGFR

The epidermal growth factor receptor (EGFR/erbB1; HER1 in humans) is a transmembrane protein, which is a member of the tyrosine kinase (RTK) receptor family that includes HER2/neu (erbB2), erbB3, and erbB4. The ErbB receptors are expressed at the cell surface and share a common structure composed of an extracellular ligand-binding domain, transmembrane segment, and an intracellular tyrosine kinase domain. The EGFR plays important roles in many biological processes including cell proliferation, metastasis, and angiogenesis, and it is overexpressed in a large proportion of epithelial tumors such as NSCLC, GBM, HNSCC, breast cancer, and colorectal cancers. Besides, EGFR also involves in other diseases including inflammatory disease, monogenic disease, wound healing, and fibrosis, etc. Therefore, this driving role in malignancies has made EGFR an attractive target for disease therapy especially cancer treatment.

Fig.1 Signaling pathways and inhibitors of EGFR. (Scaltriti, 2006)

Biparatopic EGFR-targeted Bispecific Antibody

To date, anti-EGFR biparatopic antibody has been developed and shown enhanced cytotoxicity efficacy against tumor cells. For example, a biparatopic antibody with one binding domain derived from the C225 antibody and another binding domain derived from the humanized 425 (hu425) antibody, and it was built on the strand-exchange engineered domain (SEED) scaffold. This anti-EGFR biparatopic-SEED antibody showed enhanced activity compared with parental antibodies used alone and in combination, and with the corresponding monovalent anti-EGFR-SEED antibodies used alone or in combination. Thus, this anti-EGFR biparatopic antibody has enhanced combination-activity in a single molecule. Furthermore, study results suggest that the potential to cross-link the two different epitopes is an important requirement in the mechanism of enhanced combination-activity.

Based on biparatopic antibody against EGFR presenting increased anti-tumor activity, biparatopic EGFR-targeted bispecific ADC can be considered as a potential and promising therapeutic strategy for EGFR-positive cancer.

Fig.2 Diagram depicting the structures of SEED-based antibodies. (Kelton, 2012)

What Can We Do for You?

Creative Biolabs is pioneering in antibody development, chemical synthesis, and bio-conjugation technology. We aim to provide one-stop-shop custom ADCs development services targeting different biomarkers and our services include antibody and drug preparation, modification, conjugation, and validation. At present, we provide bispecific biparatopic ADCs development service targeting the EGFR antigen. If you have any specific requirements in ADCs construction, please feel free to contact us. We are looking forward to working together with your attractive projects.

References

1. Scaltriti, M.; Baselga, J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clinical Cancer Research. 2006, 12(18): 5268-5272.
2. Kelton, C.; et al. Anti-EGFR biparatopic-SEED antibody has enhanced combination-activity in a single molecule. Archives of biochemistry and biophysics. 2012, 526(2): 219-225.

For Research Use Only. NOT FOR CLINICAL USE.