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Updated: Oct 3, 2025

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
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Cleaved CDCP1 marks the spot: a neoepitope for RAS-driven cancers

Katelyn L Donahue1, Marina Pasca di Magliano2

  • 1Graduate Program in Cancer Biology and.

The Journal of Clinical Investigation
|February 15, 2022
PubMed

Insights

Researchers identified a novel cancer neoepitope from cleaved CUB domain containing protein 1 (CDCP1). This discovery enables targeted therapies for pancreatic cancer, improving treatment specificity and efficacy.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Targeting cancer cells while sparing normal cells remains a significant challenge in cancer therapy.
  • Identifying cancer-specific neoepitopes is crucial for developing precise treatments.
  • Pancreatic cancer, a deadly type, often has a low mutational burden, limiting neoantigen availability.

Purpose of the Study:

  • To investigate neoepitopes derived from proteolytic cleavage of CUB domain containing protein 1 (CDCP1).
  • To develop targeted therapeutics against cleaved CDCP1 (c-CDCP1) for pancreatic cancer treatment.

Main Methods:

  • Generated an antibody specifically targeting cleaved CDCP1 (c-CDCP1).
  • Developed drug conjugates, radioactive ion vectors, and T cell activators targeting c-CDCP1.
  • Evaluated therapeutic efficacy in vitro and in vivo models of pancreatic cancer.

Main Results:

  • The developed therapeutics demonstrated inhibition of pancreatic cancer cell growth.
  • Targeting c-CDCP1 proved effective in both in vitro and in vivo settings.
  • The study highlights the potential of proteolytic cleavage-derived neoantigens.

Conclusions:

  • Exploiting neoantigens from proteolytic cleavage offers a promising strategy for specific cancer cell targeting.
  • Targeted therapies against c-CDCP1 show potential for treating pancreatic cancer.
  • This approach may overcome challenges associated with low mutational burden in certain cancers.

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