Ajay Jain

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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; et al. (Profiled Author: Ajay Jain)

Immunology and Hematopoiesis Division, Department of Medical Oncology, Sidney Kimmel Cancer Center, Johns Hopkins Medical Institutions, 1650 Orleans Street, Baltimore, MD 21231, USA.
Cancer research 2006;66(2):1096-104.

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.

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