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Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model
Amara C Siva1, Martha A Wild, Richard E Kirkland
1Alexion Antibody Technologies, Inc., San Diego, California, USA.
Abstract:
Through a whole-cell panning approach, we previously identified a panel of antibodies that bound to prostate cancer cell surface antigens. One such antigen, CUB domain-containing protein 1 (CDCP1), was recognized by monoclonal antibody 25A11 and is a single transmembrane molecule highly expressed in several metastatic cancers as well as on CD34(+)CD133(+) myeloid leukemic blast cells. We show CDCP1 expression on prostate cancer cell lines by real-time quantitative PCR (RT-qPCR), flow cytometry, and immunohistochemistry and on prostate cancer patient samples by RT-qPCR and immunohistochemical staining. In cell-based assays, antibody 25A11 inhibited prostate cancer cell migration and invasion in vitro. Further characterization showed that CDCP1 is internalized on antibody binding. When 25A11 was coupled to the cytotoxin saporin either directly or via a secondary antibody, both resulted in prostate cancer cell killing in vitro. In vivo targeting studies with an anti-CDCP1 immunotoxin showed significant inhibition of primary tumor growth as well as metastasis in a mouse xenograft model. These data provide support for continued evaluation of anti-CDCP1 therapy for potential use in cancer in primary and metastatic disease.
Insights
Researchers identified CUB domain-containing protein 1 (CDCP1) as a target for prostate cancer therapy. An antibody targeting CDCP1 inhibited cancer cell migration and invasion, and an immunotoxin showed efficacy in preclinical models.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Prostate cancer cell surface antigens are targets for novel therapeutics.
- CUB domain-containing protein 1 (CDCP1) is a transmembrane molecule highly expressed in metastatic cancers and myeloid leukemic cells.
Purpose of the Study:
- To investigate the role of CDCP1 in prostate cancer.
- To evaluate the therapeutic potential of targeting CDCP1 with antibody 25A11 and immunotoxins.
Main Methods:
- Whole-cell panning to identify antibodies against prostate cancer antigens.
- RT-qPCR, flow cytometry, and immunohistochemistry to confirm CDCP1 expression.
- In vitro cell-based assays for migration, invasion, and cytotoxicity.
- In vivo mouse xenograft model for tumor growth and metastasis inhibition.
Main Results:
- CDCP1 is expressed on prostate cancer cell lines and patient samples.
- Antibody 25A11 inhibited prostate cancer cell migration and invasion.
- Anti-CDCP1 immunotoxins demonstrated significant in vitro and in vivo efficacy against prostate cancer.
- CDCP1 internalization was observed upon antibody binding.
Conclusions:
- CDCP1 is a promising therapeutic target for prostate cancer.
- Targeting CDCP1 with antibody-based therapies, including immunotoxins, shows potential for treating primary and metastatic prostate cancer.
