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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2008

01-09-2008 | Original Article

Anti-tumor activity and trafficking of self, tumor-specific T cells against tumors located in the brain

Authors: Robert M. Prins, Chengyi J. Shu, Caius G. Radu, Dan D. Vo, Haumith Khan-Farooqi, Horacio Soto, Meng-Yin Yang, Muh-Shi Lin, Stephanie Shelly, Owen N. Witte, Antoni Ribas, Linda M. Liau

Published in: Cancer Immunology, Immunotherapy | Issue 9/2008

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Abstract

It is commonly believed that T cells have difficulty reaching tumors located in the brain due to the presumed “immune privilege” of the central nervous system (CNS). Therefore, we studied the biodistribution and anti-tumor activity of adoptively transferred T cells specific for an endogenous tumor-associated antigen (TAA), gp100, expressed by tumors implanted in the brain. Mice with pre-established intracranial (i.c.) tumors underwent total body irradiation (TBI) to induce transient lymphopenia, followed by the adoptive transfer of gp10025–33-specific CD8+ T cells (Pmel-1). Pmel-1 cells were transduced to express the bioluminescent imaging (BLI) gene luciferase. Following adoptive transfer, recipient mice were vaccinated with hgp10025–33 peptide-pulsed dendritic cells (hgp10025–33/DC) and systemic interleukin 2 (IL-2). This treatment regimen resulted in significant reduction in tumor size and extended survival. Imaging of T cell trafficking demonstrated early accumulation of transduced T cells in lymph nodes draining the hgp10025–33/DC vaccination sites, the spleen and the cervical lymph nodes draining the CNS tumor. Subsequently, transduced T cells accumulated in the bone marrow and brain tumor. BLI could also detect significant differences in the expansion of gp100-specific CD8+ T cells in the treatment group compared with mice that did not receive either DC vaccination or IL-2. These differences in BLI correlated with the differences seen both in survival and tumor infiltrating lymphocytes (TIL). These studies demonstrate that peripheral tolerance to endogenous TAA can be overcome to treat tumors in the brain and suggest a novel trafficking paradigm for the homing of tumor-specific T cells that target CNS tumors.
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Metadata
Title
Anti-tumor activity and trafficking of self, tumor-specific T cells against tumors located in the brain
Authors
Robert M. Prins
Chengyi J. Shu
Caius G. Radu
Dan D. Vo
Haumith Khan-Farooqi
Horacio Soto
Meng-Yin Yang
Muh-Shi Lin
Stephanie Shelly
Owen N. Witte
Antoni Ribas
Linda M. Liau
Publication date
01-09-2008
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 9/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0461-1

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