Theranostic Targeting of CUB Domain Containing Protein 1 (CDCP1) in Pancreatic Cancer.

Journal Article (Journal Article)

Purpose

The recent emergence of radioligand therapies for cancer treatment has increased enthusiasm for developing new theranostic strategies coupling both imaging and cytotoxicity in the same entity. In this study, we evaluated whether CUB domain containing protein 1 (CDCP1), a single-pass transmembrane protein highly overexpressed in diverse human cancers, might be a target for cancer theranostics.

Experimental design

The ectodomain of CDCP1 was targeted using radiolabeled forms of 4A06, a potent and specific recombinant human antibody that we developed. Imaging and antitumor assessment studies were performed in animal models of pancreatic cancer, including two patient-derived xenograft models we developed for this study. For antitumor assessment studies, the endpoints were death due to tumor volume >3,000 mm3 or ≥20% loss in body weight. Specific tracer binding or antitumor effects were assessed with an unpaired, two-tailed Student t test and survival advantages were assessed with a log rank (Mantel-Cox) test. Differences at the 95% confidence level were interpreted to be significant.

Results

89 Zr-4A06 detected a broad dynamic range of full length or cleaved CDCP1 expression on seven human pancreatic cancer tumors (n = 4/tumor). Treating mice with single or fractionated doses of 177 Lu-4A06 significantly reduced pancreatic cancer tumor volume compared with mice receiving vehicle or unlabeled 4A06 (n = 8; P < 0.01). A single dose of 225 Ac-4A06 also inhibited tumor growth, although the effect was less profound compared with 177 Lu-4A06 (n = 8; P < 0.01). A significant survival advantage was imparted by 225 Ac-4A06 (HR = 2.56; P < 0.05).

Conclusions

These data establish that CDCP1 can be exploited for theranostics, a finding with widespread implications given its breadth of overexpression in cancer.

Full Text

Duke Authors

Cited Authors

  • Moroz, A; Wang, Y-H; Sharib, JM; Wei, J; Zhao, N; Huang, Y; Chen, Z; Martinko, AJ; Zhuo, J; Lim, SA; Zhang, LH; Seo, Y; Carlin, S; Leung, KK; Collisson, EA; Kirkwood, KS; Wells, JA; Evans, MJ

Published Date

  • July 2020

Published In

Volume / Issue

  • 26 / 14

Start / End Page

  • 3608 - 3615

PubMed ID

  • 32341034

Pubmed Central ID

  • PMC7367754

Electronic International Standard Serial Number (EISSN)

  • 1557-3265

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.ccr-20-0268

Language

  • eng