ArticleCancer chemotherapy and pharmacology2026
CDCP1-targeted antibody-drug conjugates and immunocytokines for cancer therapy.
Article in Cancer chemotherapy and pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeCUB 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).
methodsNovel 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.
resultsCDCP1 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.
conclusionThese findings established CDCP1 as a versatile therapeutic target and supported further development of parallel CDCP1-targeted ADC and immunocytokine strategies for solid tumors.
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