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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 Article has an altmetric score of 39

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 4

Quantitative Immuno-PET tracer pharmacokinetics and biodistribution.

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Quantitative Immuno-PET tracer pharmacokinetics and biodistribution.
(A)...
(A) Early (day 2) post-therapy 64Cu-DOTA-AbOX40 uptake profile (fold change: % ID/g ROI/% ID/g muscle; no PVC) in CpG-treated (n = 7) versus vehicle-treated (Veh) (n = 7) mice 24 hours after injection (100 μCi). Sp, spleen; Ax, axillary LN; Pop, popliteal LN; Ing, inguinal LN; Mus, muscle; Br, brain. Two distinct clusters of image biomarkers, labeled 1 and 2, were identified from unsupervised hierarchical clustering. (B) 64Cu-DOTA-AbOX40 pharmacokinetic uptake and clearance (% ID/g) in CpG-treated (n = 3) versus vehicle-treated (n = 3) mouse cohorts 2, 16, and 24 hours after injection (p.i.). (C) Early (day 2) 64Cu-DOTA-AbOX40 biodistribution (BIOD) uptake (% ID/g) in treated tumors versus untreated tumors and background muscle. (D) Early (day 2) 64Cu-DOTA-AbOX40 biodistribution uptake in spleen (% ID/g, % ID/spleen). (E) Early (day 2) tumor response (% change in volume) versus day-2 tumor 64Cu-DOTA-AbOX40 uptake (% ID/g BIOD). Generalized linear regression was applied. CpG: y = –10.3x + 115.3, R2 = 0.9141; vehicle: y = 22.2x – 54.1, R2 = 0.06; y axis 1: yellow/CpG, y axis 2: blue/vehicle. (F and G) Late (day 9) 64Cu-DOTA-AbOX40 uptake in tumors, spleen, and muscle (% ID/g, % ID/spleen, BIOD). (H) Late (day 9) uptake in left and right axillary LNs of individual CpG- and vehicle-treated mice (% ID/g, BIOD). All values represent the mean ± SEM. ****P < 0.0001, **P < 0.01, and *P < 0.05, by 2-way ANOVA with Bonferroni’s post hoc test for multiple comparisons or by Student’s t test.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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