Molecular imaging biomarker predicts response to CAR T cell therapy

Reston, VA – A new PET imaging agent, 18F-AlF-FAPI-74 has been found to effectively monitor and predict the treatment response of a promising cancer therapy. This noninvasive imaging approach has the potential to help inform important clinical decision-making at the start of treatment, including re-dosing of therapy, dose optimization, changing therapeutic course, and many more, to optimize patient outcomes. The research was presented at the 2022 annual meeting of the Society of Nuclear Medicine and Molecular Imaging.

Chimeric antigen receptor (CAR T) T cell therapy is a treatment that involves removing T cells from a patient’s body, engineering them in the laboratory, and then returning the T cells to the body to combat the specified disease. This type of therapy has had marked success in treating blood cancers, but has not been as effective in treating solid tumors.

“Our understanding of why CAR T therapies are not as effective in solid tumors could be advanced by measuring antigens targeted by CAR T, such as fibroblast activating protein (FAP), which is overproduced in many types of solid tumors,” said Iris Lee. , PhD student at the University of Pennsylvania. In this study, we used 18F-AlF-FAPI-74 PET to image FAP with the aim of providing information that could aid in the development and optimization of FAP CAR T cell therapy for solid tumors.

Several experiments were conducted as part of the study. In the first, an in vitro cellular uptake experiment was performed to test the binding of 18F-AlF-FAPI-74 tracer in FAP-expressing cells. Next, tracer uptake was assessed in two different tumor xenograft models (mesothelioma and adenocarcinoma). Finally, the researchers assessed whether 18F-AlF-FAPI-74 could detect FAP clearance as a means of monitoring treatment response of FAP CAR T cells.

The cell uptake experiment demonstrated highly specific binding of 18F-AlF-FAPI-74 to FAP. For both xenograft models, a significant increase in 18Uptake of F-AlF-FAPI-74 into the tumor was scored relative to background tissues (e.g. muscle and blood). 18F-AlF-FAPI-74 PET was also able to successfully detect and image FAP+ tumor cells following FAP CAR T cell treatment.

“Our work highlights the potential role of 18F-AlF-FAPI-74 as a predictive and pharmacodynamic imaging biomarker to guide patient selection and monitor therapeutic response to FAP-targeted therapies,” Lee noted.

She added, “In today’s era of precision medicine where cancer therapies can be tailored based on the presence or absence of a biomarker, molecular imaging tools have the potential to add value to clinical care by helping to accurately monitor the target of interest and stratify patients for certain treatments based on target expression level.

Figure 1. Representative 18F-AlF-FAPI-74 PET/CT images showed statistical differences in tracer uptake between non-transduced T cell (NTD) treated animals (left, M4916) and FAP CAR T cell treated animals (right, M4917)

Abstract 892. “Monitoring the Therapeutic Response to FAP CAR T Cells Using [18F]AlF-FAPI-74 PET,” Iris K. Lee, Department of Bioengineering and Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Estela Noguera-Ortega and Maria Liousia, Thoracic Oncology Research Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Zebin Xiao, Leslie Todd, and Ellen Puré, Department of Biomedical Sciences, School of Veterinary Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Kexiang Xu, Kimberly J. Edwards, and Mark A. Sellmyer, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and Steven Albelda, Thoracic Oncology Research Laboratory, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

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