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T cells reporting for duty
Cytotoxic T cells engineered to kill tumor cells are becoming a mainstay of cancer immunotherapy. However, no matter how precisely they are engineered, once they are injected into a patient, they are no longer directly monitored or controlled by the researchers. As a result, if the treatment fails to work or causes toxicity, it is not clear whether the therapeutic cells are ineffective or whether they scattered through normal tissues and never reached the tumor. Keu et al. have designed a method to engineer these T cells with a reporter gene such that they can be tracked in people by positron emission tomography. The authors present a clinical trial demonstrating the feasibility and safety of this approach in glioma patients.
Abstract
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.
- Copyright © 2017, American Association for the Advancement of Science
