TY - JOUR
T1 - Gene therapy to manipulate effector T cell trafficking to tumors for immunotherapy
AU - Gough, Michael
AU - Crittenden, Marka
AU - Thanarajasingam, Uma
AU - Sanchez-Perez, Luis
AU - Thompson, Jill
AU - Jevremovic, Dragan
AU - Vile, Richard
PY - 2005/5/1
Y1 - 2005/5/1
N2 - Strategies that generate tumor Ag-specific effector cells do not necessarily cure established tumors. We hypothesized that the relative efficiency with which tumor-specific effector cells reach the tumor is critical for therapy. We demonstrate in this study that activated T cells respond to the chemokine CCL3, both in vitro and in vivo, and we further demonstrate that expression of CCL3 within tumors increases the effector T cell infiltrate in those tumors. Importantly, we show that adenoviral gene transfer to cause expression of CCL3 within B16ova tumors in vivo increases the efficacy of adoptive transfer of tumor-specific effector OT1 T cells. We additionally demonstrate that such therapies result in endogenous immune responses to tumor Ags that are capable of protecting animals against subsequent tumor challenge. Strategies that modify the "visibility" of tumors have the potential to significantly enhance the efficacy of both vaccine and adoptive transfer therapies currently in development.
AB - Strategies that generate tumor Ag-specific effector cells do not necessarily cure established tumors. We hypothesized that the relative efficiency with which tumor-specific effector cells reach the tumor is critical for therapy. We demonstrate in this study that activated T cells respond to the chemokine CCL3, both in vitro and in vivo, and we further demonstrate that expression of CCL3 within tumors increases the effector T cell infiltrate in those tumors. Importantly, we show that adenoviral gene transfer to cause expression of CCL3 within B16ova tumors in vivo increases the efficacy of adoptive transfer of tumor-specific effector OT1 T cells. We additionally demonstrate that such therapies result in endogenous immune responses to tumor Ags that are capable of protecting animals against subsequent tumor challenge. Strategies that modify the "visibility" of tumors have the potential to significantly enhance the efficacy of both vaccine and adoptive transfer therapies currently in development.
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U2 - 10.4049/jimmunol.174.9.5766
DO - 10.4049/jimmunol.174.9.5766
M3 - Article
C2 - 15843579
AN - SCOPUS:17844391297
SN - 0022-1767
VL - 174
SP - 5766
EP - 5773
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -