Whole-body PET Imaging of T-cell Response to Glioblastoma

Tomomi W. Nobashi, Aaron T. Mayer, Zunyu Xiao, Carmel T. Chan, Aisling M. Chaney, Michelle L. James, Sanjiv S. Gambhir

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Purpose: Immunotherapy is a promising approach for many oncological malignancies, including glioblastoma, however, there are currently no available tools or biomarkers to accurately assess whole-body immune responses in patients with glioblastoma treated with immunotherapy. Here, the utility of OX40, a costimulatory molecule mainly expressed on activated effector T cells known to play an important role in eliminating cancer cells, was evaluated as a PET imaging biomarker to quantify and track response to immunotherapy. Experimental Design: A subcutaneous vaccination approach of CpG oligodeoxynucleotide, OX40 mAb, and tumor lysate at a remote site in a murine orthotopic glioma model was developed to induce activation of T cells distantly while monitoring their distribution in stimulated lymphoid organs with respect to observed therapeutic effects. To detect OX40-positive T cells, we utilized our in-house-developed 89Zr-DFO-OX40 mAb and in vivo PET/CT imaging. Results: ImmunoPET with 89Zr-DFO-OX40 mAb revealed strong OX40-positive responses with high specificity, not only in the nearest lymph node from vaccinated area (mean, 20.8%ID/cc) but also in the spleen (16.7%ID/cc) and the tumor draining lymph node (11.4%ID/cc). When the tumor was small (<106 p/sec/cm2/sr in bioluminescence imaging), a high number of responders and percentage shrinkage in tumor signal was indicated after only a single cycle of vaccination. Conclusions: The results highlight the promise of clinically translating cancer vaccination as a potential glioma therapy, as well as the benefits of monitoring efficacy of these treatments using immunoPET imaging of T-cell activation. _2021 American Association for Cancer Research.

Original languageEnglish
Pages (from-to)6445-6456
Number of pages12
JournalClinical Cancer Research
Volume27
Issue number23
DOIs
StatePublished - Dec 1 2021

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