Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo

Robert D. Loberg, Chi Ying, Matt Craig, Lashon L. Day, Erin Sargent, Chris Neeley, Kirk Wojno, Linda A. Snyder, Li Yan, Kenneth J. Pienta

Research output: Contribution to journalArticle

Abstract

The identification of novel tumor-interactive chemokines and the associated insights into the molecular and cellular basis of tumor-microenvironment interactions have continued to stimulate the development of targeted cancer therapeutics. Recently, we have identified monocyte chemoattractant protein 1 (MCP-1; CCL2) as a prominent regulator of prostate cancer growth and metastasis. Using neutralizing antibodies to human CCL2 (CNTO888) and the mouse homologue CCL2/JE (C1142), we show that treatment with anti-CCL2/JE antibody (2 mg/kg, twice weekly i.p.) attenuated PC-3Luc-mediated overall tumor burden in our in vivo model of prostate cancer metastasis by 96% at 5 weeks postintracardiac injection. Anti-CCL2 inhibition was not as effective as docetaxel (40 mg/kg, every week for 3 weeks) as a single agent, but inhibition of CCL2 in combination with docetaxel significantly reduced overall tumor burden compared with docetaxel alone, and induced tumor regression relative to initial tumor burden. These data suggest an interaction between tumor-derived chemokines and host-derived chemokines acting in cooperation to promote tumor cell survival, proliferation, and metastasis.

Original languageEnglish (US)
Pages (from-to)9417-9424
Number of pages8
JournalCancer Research
Volume67
Issue number19
DOIs
StatePublished - Oct 1 2007

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Loberg, R. D., Ying, C., Craig, M., Day, L. L., Sargent, E., Neeley, C., Wojno, K., Snyder, L. A., Yan, L., & Pienta, K. J. (2007). Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo. Cancer Research, 67(19), 9417-9424. https://doi.org/10.1158/0008-5472.CAN-07-1286