Selective targeting of antitumor immune responses with engineered live-attenuated Listeria monocytogenes

Kiyoshi Yoshimura, Ajay Jain, Heather E. Allen, Lindsay S. Laird, Christina Y. Chia, Sowmya Ravi, Dirk G. Brockstedt, Martin A. Giedlin, Keith S. Bahjat, Meredith L. Leong, Jill E. Slansky, David N. Cook, Thomas W. Dubensky, Drew M. Pardoll, Richard D. Schulick

Research output: Contribution to journalArticlepeer-review

Abstract

Improved immunization and ex vivo T-cell culture strategies can generate larger numbers and more potent tumor-specific effector cells than previously possible. Nonetheless, the capacity of these cells to eliminate established tumors is limited by their ability to efficiently enter tumor-bearing organs and mediate their effector function. In the current study, we show that the administration of an engineered organ-homing microbe selectively targets tumor-specific immune responses to metastases within that organ. Specifically, an attenuated Listeria monocytogenes strain, which preferentially infects the liver following systemic administration, dramatically enhances the activity of a cancer vaccine against liver metastases but not metastases in the lung. This enhanced activity results from both local recruitment of innate immune effectors as well as concentration and increased activation of vaccine-induced antitumor T cells within the liver. These findings show a general approach to focus systemic cancer immunotherapies to specific organs bearing tumor metastases by taking advantage of differential tropisms and the proinflammatory nature of microbes.

Original languageEnglish (US)
Pages (from-to)1096-1104
Number of pages9
JournalCancer Research
Volume66
Issue number2
DOIs
StatePublished - Jan 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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