Lung Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Cancer, including details on symptoms, smoking, genetics, treatment, causes.

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

Yoshimura K, Jain A, Allen HE, Laird LS, Chia CY, Ravi S, Brockstedt DG, Giedlin MA, Bahjat KS, Leong ML, Slansky JE, Cook DN, Dubensky TW, Pardoll DM, Schulick RD

Immunology and Hematopoiesis Division, Department of Medical Oncology, Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.

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.

Published 20 January 2006 in Cancer Res, 66(2): 1096-104.
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