Immunotheranostics in Solid Tumors: Longitudinal Tracking of Human IL13Ra2 CAR-T Cells In Vivo
Year: 2025
Type: article
Abstract: Chimeric antigen receptor (CAR)-T cell therapy has shown limited success in the treatment of solid tumors, reinforcing the need to elucidate the in vivo biodistribution of these engineered T cells. Here, we integrate the anti-DOTA huC825 reporter (“Thor”) platform into newly developed human anti–interleukin-13 receptor α-2 (IL13Rα2)–single-cell fragment variable (scFv)–derived CAR-T cells and investigate its utility for mapping CAR-T cell distribution in a xenograft mouse model of melanoma. Methods: We engineered anti–IL13Rα2-scFv–derived CAR-T cells expressing huC825 (KLG3BBz-huC825), evaluated detection sensitivity, and monitored CAR-T cell biodistribution via weekly [86Y]Y-aminobenzyl-DOTA PET/CT and therapeutic efficacy. Results: KLG3BBz-huC825 T cells demonstrated potent antigen-specific cytotoxicity and cytokine release in vitro. The Thor radiohapten capture platform offered exquisite detection sensitivity of only 3,000 engineered T cells and enabled prolonged spatiotemporal assessment of CAR-T cell kinetics up to 7 wk after infusion, corroborated by histopathology. Treatment with KLG3BBz-huC825 resulted in an overall survival benefit. Conclusion: The Thor platform offers a versatile and highly sensitive approach to study the real-time kinetics of CAR-T cells in vivo.
Source: Journal of Nuclear Medicine
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Targeting Drug-Resistant Castration Resistant Prostate Cancer via LIMK2, Cancer Center Support Grant, Understanding and Mimicking TCR Recognition with Therapeutic Monoclonal Antibodies., IL13Ra2-targeted radioimmunotherapy for glioblastoma, SPORE in Brain Cancer, Interrogating the in vivo pharmacokinetics of armored CARs with radiohapten capture
OpenAlex ID: W7117589352