Doer Biologics’Trispecific Antibody DR30206 Preclinical Research Published in International Immunopharmacology

2024.02.22

On February 21, 2024, Zhejiang Doer Biologics Co., Ltd.(Doer Biologics) published preclinical research findings on its self-developed trispecific antibody DR30206 in the highly influential immunology and pharmacology journal International Immunopharmacology (2024 JCR Impact Factor 5.7). The article is titled "An innovative antibody fusion protein targeting PD-L1, VEGF and TGF-β with enhanced antitumor efficacies." Dr. Huang Yanshan, Founder and CEO of Doer Biologics, serves as the corresponding author.

Immunosuppression within the tumor microenvironment (TME) is closely linked to tumor progression. Programmed death ligand/receptor (PD-L1/PD-1), vascular endothelial growth factor (VEGF), and transforming growth factor beta (TGF-β) jointly participate in the regulation of the TME. Monotherapy with immune checkpoint inhibitors (ICIs, such as PD-1/PD-L1 antibodies) often leads to immune escape, while combination therapies frequently result in high toxicity and side effects. DR30206, a trispecific antibody fusion protein, was designed to enhance the immune response by targeting PD-L1 on the basis of monomeric antibody, while simultaneously inhibiting VEGF and TGF-β within the TME using a single molecule, thereby achieving potent suppression of tumor growth.

The structural design of DR30206 was based initially on Doer Biologics' proprietary SMART-VHHBody platform technology, which enabled the screening and identification of a single-domain antibody sequence specifically targeting PD-L1. The anti-PD-L1 single-domain antibody and the TGF-β receptor were then fused to the N-terminus and C-terminus, respectively, of the VEGF antibody Bevacizumab, forming the trispecific antibody fusion protein structure.

DR30206 exhibits high affinity and blocking activity against the VEGF, TGF-β, and PD-L1 targets. It demonstrated superior antitumor efficacy and favorable nonclinical safety profiles in multiple humanized tumor-bearing mouse models, indicating its significant potential value for clinical development. DR30206 has currently entered Phase I clinical studies. (Refer to Doer Biologics’ official WeChat article published on December 5, 2023, titled " Doer Biologics Announces Completion of First Patient Dosing in Chinese Phase I Clinical Trial for DR30206" for specifics.)

Full text access link: https://doi.org/10.1016/j.intimp.2024.111698