TY - JOUR
T1 - An effective immuno-PET imaging method to monitor CD8-dependent responses to immunotherapy
AU - Tavaré, Richard
AU - Escuin-Ordinas, Helena
AU - Mok, Stephen
AU - McCracken, Melissa N.
AU - Zettlitz, Kirstin A.
AU - Salazar, Felix B.
AU - Witte, Owen N.
AU - Ribas, Antoni
AU - Wu, Anna M.
N1 - Publisher Copyright:
© 2015 AACR.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity of noninvasive and quantitative technologies capable of monitoring the presence and abundance of CD8+ T cells and other immune cell subsets. In this study, we describe the generation of 89Zr-desferrioxamine-labeled anti- CD8 cys-diabody (89Zr-malDFO-169 cDb) for noninvasive immuno-PET tracking of endogenous CD8+ T cells. We demonstrate that anti-CD8 immuno-PET is a sensitive tool for detecting changes in systemic and tumor-infiltrating CD8 expression in preclinical syngeneic tumor immunotherapy models including antigen-specific adoptive T-cell transfer, agonistic antibody therapy (anti-CD137/4-1BB), and checkpoint blockade antibody therapy (anti-PD-L1). The ability of anti-CD8 immuno-PET to provide whole body information regarding therapy-induced alterations of this dynamic T-cell population provides new opportunities to evaluate antitumor immune responses of immunotherapies currently being evaluated in the clinic.
AB - The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity of noninvasive and quantitative technologies capable of monitoring the presence and abundance of CD8+ T cells and other immune cell subsets. In this study, we describe the generation of 89Zr-desferrioxamine-labeled anti- CD8 cys-diabody (89Zr-malDFO-169 cDb) for noninvasive immuno-PET tracking of endogenous CD8+ T cells. We demonstrate that anti-CD8 immuno-PET is a sensitive tool for detecting changes in systemic and tumor-infiltrating CD8 expression in preclinical syngeneic tumor immunotherapy models including antigen-specific adoptive T-cell transfer, agonistic antibody therapy (anti-CD137/4-1BB), and checkpoint blockade antibody therapy (anti-PD-L1). The ability of anti-CD8 immuno-PET to provide whole body information regarding therapy-induced alterations of this dynamic T-cell population provides new opportunities to evaluate antitumor immune responses of immunotherapies currently being evaluated in the clinic.
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U2 - 10.1158/0008-5472.CAN-15-1707
DO - 10.1158/0008-5472.CAN-15-1707
M3 - Article
C2 - 26573799
AN - SCOPUS:84958953141
SN - 0008-5472
VL - 76
SP - 73
EP - 82
JO - Cancer Research
JF - Cancer Research
IS - 1
ER -