The 2026 Annual Meeting of the American Association for Cancer Research (AACR) will be held April 17–22 at the San Diego Convention Center in California, USA. Doer Biologics will present the latest preclinical research findings on the DR319-DP (Nectin-4/Trop-2 dual-toxin ADC) project at the meeting.
DR319: Nectin-4/Trop-2 bispecific ADC
Although Trop-2 and Nectin-4 are highly promising targets for next-generation antibody-drug conjugates (ADCs), the emergence of drug resistance, along with toxicities arising from both "off-target/off-tumor" and "on-target/off-tumor" effects, remain significant therapeutic challenges. To maximize anti-tumor activity while reducing systemic toxicity and broadening the therapeutic window, this study developed a "1+1" configuration, avidity-driven bispecific antibody-DR319, in which the anti-Trop-2 VHH is a monovalent, low-affinity binding arm. This design enables strong binding to Nectin-4/Trop-2 double-positive tumor cells while reducing binding to single-positive cells, thereby decreasing peripheral toxicity.
The researchers conjugated DR319 with a novel linker-topoisomerase I inhibitor (Topo I) payload, CPD3, to generate DR319-CPD3. In mouse models, DR319-CPD3 demonstrated superior anti-tumor activity compared to single-target ADCs. Furthermore, using a glycan-conjugated dual-payload platform (YT-DP), the team constructed a dual-payload ADC-DR319-DP. DR319-DP employs a payload combination of a topoisomerase I inhibitor (Topo I) at DAR 4 and a microtubule inhibitor (MTI) at DAR 2. In preclinical studies, the dual-mechanism-of-action (MOA) payloads of DR319-DP achieved more potent and durable tumor inhibition than single-target/single-payload benchmark ADCs across multiple CDX and PDX tumor models. These preclinical results strongly support the clinical development of the DR319 series of ADCs and their potential to become a best-in-class therapy for the treatment of solid tumors.
Poster Information
Abstract Title: DR319-DP: A Nectin-4/Trop-2 bispecific ADC with an avidity-driven VHH design and dual-MOA payloads
Presentation Format: Poster
Presentation Location: Poster Section 16
Presentation Time: April 21, 2026 (Tuesday), 9:00 AM – 12:00 PM (Pacific Time)
Abstract Number: 4541