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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

Imaging activated T cells predicts response to cancer vaccines

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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 3

Noninvasive imaging of OX40 captures the spatiotemporal dynamics of activated T cells following in situ vaccination.

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Noninvasive imaging of OX40 captures the spatiotemporal dynamics of acti...
Images were acquired 24 hours after 64Cu-DOTA-AbOX40 tracer injection (~100 μCi). (A) Reference atlas for image ROIs. TT DLN, treated TDLN; UT DLN, untreated TDLN; H, heart; Li, liver; Bl, bladder. (B) Top: Head-on view of volume-rendered technique (VRT) PET-CT images of representative mice vaccinated in situ with either vehicle or CpG. Bottom: Axial cross section through tumors and heart. Images were acquired on day 2 after therapy. VRT PET-CT images of representative vehicle-treated (C) and CpG-treated (D) mice on days 2 and 9 after vaccination. White arrows indicate the treatment site. Scale bar: Maximum (Max) = red; minimum (Min) = green.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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