CDCP1-targeted antibody-drug conjugates and immunocytokines for cancer therapy.

Authors

Guangmao Mu, Mingcan Yu, Fulai Zhou, Honglei Bi, Zhengxia Zha, Sheng Huang, Ying Jin, Chao Han, Mark L Chiu, Di Zhang

Published in

Cancer chemotherapy and pharmacology. Volume 96. Issue 1. Aug 17, 2026. Epub Aug 17, 2026.

Abstract

CUB domain-containing protein 1 (CDCP1) is an emerging tumor-associated surface antigen broadly expressed in solid tumors and linked to poor prognosis, making it an attractive target for selective therapeutic delivery. We evaluated CDCP1 as a platform for two distinct therapeutic modalities: an antibody-drug conjugate (ADC) for cytotoxic payload delivery and an immunocytokine for targeted delivery of interferon-α2b (IFNα2b).
Novel humanized anti-CDCP1 monoclonal antibodies were generated and characterized for binding to recombinant and cell-surface CDCP1. CDCP1 expression in tumor cells and xenografts was assessed by flow cytometry and immunohistochemistry. CDCP1-targeted ADCs and CDCP1-targeted IFNα2b fusion proteins, including attenuated IFNα2b variants, were evaluated for in vitro cytotoxicity and in vivo antitumor activity in multiple solid tumor xenograft models. A murine cross-reactive anti-CDCP1 ADC was further assessed in an acute mouse toxicity study.
CDCP1 was broadly expressed across multiple solid tumor cell lines and xenografts. CDCP1-targeted ADCs mediated potent, target-dependent cytotoxicity in vitro, and MMAE-conjugated ADCs showed robust antitumor activity in pancreatic, lung, breast, and colon xenograft models, with tumor growth inhibition up to 90%. Antibodies recognizing the proteolyzed amino-terminal region of CDCP1 also retained in vivo activity. The murine cross-reactive ADC was well tolerated in an acute toxicity study. CDCP1-targeted IFNα2b fusion proteins displayed markedly enhanced potency against CDCP1-positive tumor cells versus a non-targeted control, and IFNα2b attenuation enabled tunable cytokine activity. In a human PBMC-supported BxPC-3 model, a CDCP1-targeted IFNα2b immunocytokine achieved significant tumor growth inhibition.
These findings established CDCP1 as a versatile therapeutic target and supported further development of parallel CDCP1-targeted ADC and immunocytokine strategies for solid tumors.

PMID:
42604889
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.