ADC Development Services Targeting EGFRvIII

With improved understanding of the molecular pathways that drive malignancy in glioblastoma, various biomarkers have been identfied and several therapeutic strategies targeting specific molecular pathways in malignant cells are under active development. Antibody-drug conjugates (ADCs), particularly anti-epidermal growth factor receptor variant III (EGFRvIII)-based constructs, are a highly promising new treatment approach for patients with glioblastoma. Creative Biolabs is a pioneer and undisputed global leader in the rapidly emerging market for ADC development. We now offer a full range of customized anti-EGFRvIII ADC development services and the off-the-shelf Anti- EGFRvIII ADC Product to support your research of glioblastoma.

Introduction of EGFRvIII

Sequencing of glioblastoma by The Cancer Genome Atlas (TCGA) effort and others is generating a clearer picture of the molecular basis of glioblastoma. The TCGA determined that the alteration of EGFR is almost exclusively observed in the classical subtype of glioblastoma. The most common genetic alteration found in glioblastoma is EGFRvIII wherein exons 2 to 7 of EGFR have been deleted. Deletion of EGFR's exons 2 to 7 yields a protein that is incapable of binding to EGFR ligands but remains constitutively activate leading to a malignant phenotype. EGFRvIII expression in glioblastoma samples is reported between 25% to 50%, depending on the method used for detection. At present, there is no evidence of EGFRvIII expression in wild-type human tissues; thus, EGFRvIII serves as a unique tumor-specific antigen and is a promising candidate for targeted therapy of glioblastoma.

Fig.1 Epidermal growth factor receptor and EGFRvIII. (An, 2018)

Anti-EGFRvIII ADC in Glioblastoma

EGFRvIII is expressed in tumors, and its lack of normal tissue expression makes it an ideal candidate for pursuing a targeted therapeutic. AMG 595 is a ADC with a tumor‑specific anti‑EGFRvIII antibody conjugated to the maytansinoid DM1, via a non‑cleavable linker. Patients with glioblastoma positive for EGFRvIII expression (one‑third of patients with glioblastoma) are the subgroup that would potentially benefit from treatment with this ADC. And AMG 595 has shown promising preclinical activity in assays including orthotopic murine models. Besides, a phase I/II study of AMG 595 in patients with recurrent glioblastoma is underway.

Fig.2 Schematic representation of AMG 595. (Hamblett, 2015)

What Can We Do for You?

The tumor-specific nature of EGFRvIII, internalization, and minimal potency as an unmodified anti-EGFRvIII antibody make EGFRvIII an attractive target to explore with a selective ADC. With the help of our ADC Antibody Screening Platform, Creative Biolabs is capable of generating a series of antibodies that binds solely to EGFRvIII and does not bind to wild-type EGFR. Through our innovative Antibody Design and Conjugation as well as DrugLnk™ Custom Synthesis platforms, these humanized or fully human anti-EGFRvIII-specific mAbs can be conjugated to the appropriate payload, via the non-cleavable or cleavable linker to generate customized ADCs. In addition, a series of ADC in vivo Analysis and ADC in vitro Analysis services can be performed upon request.

Creative Biolabs has gained significant knowledge in ADC preparation and we are more than happy to share our experience and help our clients with this tragically important step in drug development. Please contact us for more information and a detailed quote.

References

1. An, Z.; et al. Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies. Oncogene. 2018, 37(12): 1561.
2. Hamblett, K.; et al. AMG 595, an anti-EGFRvIII antibody-drug conjugate, induces potent antitumor activity against EGFRvIII-expressing glioblastoma. Molecular cancer therapeutics. 2015, 14(7): 1614-1624.

For Research Use Only. NOT FOR CLINICAL USE.