What question did this study set out to answer?

The aim is to evaluate the efficacy of a newly developed ADC targeting CDCP1 in cancer treatment.

April 5, 2026

Abstract 6937: BCG046, a CDCP1 ADC that targets CTF, has demonstrated potent in vitro and in vivo efficacy

HWHaochen WeiJohns Hopkins University NZNa ZhangBeijing Biocytogen (China)CSChengzhang ShangBeijing Biocytogen (China)

Key Points

The aim is to evaluate the efficacy of a newly developed ADC targeting CDCP1 in cancer treatment.
Developed antibody clone Ab.168 targeting CTF of CDCP1 using RenMice platform.
Tested Ab.168 for binding affinity in various tumor cell lines.
Evaluated binding activity under stress conditions and assessed nonspecific binding.
Conjugated Ab.168 with vcMMAE and tested in NSCLC and colorectal PDX models.
Ab.168 exhibited strong binding to tumor cell lines with varying CDCP1 levels.
Demonstrated effective internalization comparable to benchmark fragments.
ADC combination with vcMMAE showed superior efficacy in PDX models compared to existing ADCs.

Abstract

Abstract Background CUB domain-containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is associated with tumor progression, drug resistance, and a poor prognosis. CDCP1 is highly expressed in various types of cancer, including pancreatic, breast, prostate, ovarian, colorectal, and lung cancers. It is closely tied to patient prognosis. CDCP1 can be cleaved by extracellular proteases, resulting in the shedding of the protein. The presence of these shedding CDCP1 in the serum of cancer patients raises concerns regarding the neutralization of biologic therapeutics. Results Thus, we developed the antibody clone Ab.168, which specifically targets the C-terminal fragment (CTF) of CDCP1, utilizing our fully human RenMice platform. Ab.168 exhibited cross-reactivity with human, monkey, and mouse CDCP1, demonstrating a strong affinity for and effective binding to a variety of tumor cell lines. This broad reactivity underscores its potential for use in preclinical development and transition. Additionally, it displayed efficient internalization in cell lines with varying levels of CDCP1 expression, with performance comparable to or better than both the CTF and amino-terminal fragment (ATF) benchmarks. Moreover, Ab.168 exhibited robust development potential, as its binding activity remained unaffected by stress conditions, and it showed no nonspecific binding in polyreaction assays. When conjugated to vcMMAE, Ab.168-vcMMAE demonstrated superior or comparable efficacy to benchmark ADCs in NSCLC and colorectal patient-derived xenograft (PDX) models. Conclusion These findings underscore the therapeutic potential of Ab.168 in developing an ADC as a promising strategy for treating colorectal cancer and other solid tumors characterized by CDCP1 expression. Further preclinical studies are underway. Citation Format: Haochen Wei, Na Zhang, Chengzhang Shang, Yi Yang, . BCG046, a CDCP1 ADC that targets CTF, has demonstrated potent in vitro and in vivo efficacy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6937.

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