Imaging activated T cells predicts response to cancer vaccines

In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies. Intratumoral vaccine administration is thought to activate a T cell-mediated immune response, which begins in the treated tumor and cascades systemical...

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Bibliographic Details
Published in:The Journal of clinical investigation 2018-06, Vol.128 (6), p.2569-2580
Main Authors: Alam, Israt S, Mayer, Aaron T, Sagiv-Barfi, Idit, Wang, Kezheng, Vermesh, Ophir, Czerwinski, Debra K, Johnson, Emily M, James, Michelle L, Levy, Ronald, Gambhir, Sanjiv S
Format: Article
Language:English
Subjects:
Analysis
Antigens
Biological markers
Biomarkers
Biomedical research
Biopsy
Cancer
Cancer immunotherapy
Cancer treatment
Cancer vaccines
Cell activation
Cell surface
CpG islands
Disease
Immune response (cell-mediated)
Immunotherapy
Kinases
Lymphocytes
Lymphocytes T
Metabolism
Multiple sclerosis
Positron emission tomography
Surface markers
T cell receptors
T cells
Tumor necrosis factor
Tumors
Vaccines
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Summary:In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies. Intratumoral vaccine administration is thought to activate a T cell-mediated immune response, which begins in the treated tumor and cascades systemically. In this study, we describe a PET tracer (64Cu-DOTA-AbOX40) that enabled noninvasive and longitudinal imaging of OX40, a cell-surface marker of T cell activation. We report the spatiotemporal dynamics of T cell activation following in situ vaccination with CpG oligodeoxynucleotide in a dual tumor-bearing mouse model. We demonstrate that OX40 imaging was able to predict tumor responses on day 9 after treatment on the basis of tumor tracer uptake on day 2, with greater accuracy than both anatomical and blood-based measurements. These studies provide key insights into global T cell activation following local CpG treatment and indicate that 64Cu-DOTA-AbOX40 is a promising candidate for monitoring clinical cancer immunotherapy strategies.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI98509