Imaging activated T cells predicts response to cancer vaccines
Israt S. Alam, … , Ronald Levy, Sanjiv S. Gambhir
Israt S. Alam, … , Ronald Levy, Sanjiv S. Gambhir
Published March 29, 2018
Citation Information: J Clin Invest. 2018;128(6):2569-2580. https://doi.org/10.1172/JCI98509.
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Research Article Immunology Oncology Article has an altmetric score of 39

Imaging activated T cells predicts response to cancer vaccines

Abstract

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.

Authors

Israt S. Alam, Aaron T. Mayer, Idit Sagiv-Barfi, Kezheng Wang, Ophir Vermesh, Debra K. Czerwinski, Emily M. Johnson, Michelle L. James, Ronald Levy, Sanjiv S. Gambhir

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Figure 5

Imaging- and blood-based correlates of response to in situ tumor vaccination with CpG.

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Imaging- and blood-based correlates of response to in situ tumor vaccina...
(A) Correlelogram of top hits determined by significance analysis of microarrays from a Luminex 38 plex cytokine assay (fold change; MFI/control) and Immuno-PET imaging ROIs (fold change; % ID/g ROI/muscle) with tumor response on day 2: log(fold[tumor volume mm3 on day 2/tumor volume mm3 on day 0]). Color scale and circle size both represent Pearson’s correlation coefficients. Large yellow circle (–1) indicates perfect inverse correlation; no circle (0) indicates no correlation; large blue circle (1) indicates perfect correlation. (B) Univariate regression of day-9 tumor response versus day-2 tumor response according to anatomical measurements. (C) Univariate regression of day-9 tumor response versus day-2 tumor tracer uptake (% ID/g). Blue line indicates vehicle-only fit; yellow line indicates CpG-only fit; black dashed line indicates all. (D) Tumor growth versus time after therapy. Yellow zone designates responders. The cutoff was determined using unsupervised hierarchical clustering. (E) Unsupervised hierarchical clustering and model visualization of the k-means nearest-centroid classifier. Lines indicate predictions; circles indicate truth.