Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging
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Summary
This summary is machine-generated.Engineered T cells expressing a novel PET reporter (hdCK3mut) enable noninvasive tracking of adoptive cell therapy, ensuring tumor homing and reducing off-tumor risks in immunotherapy research.
Area Of Science
- Immunotherapy
- Molecular Imaging
- Cellular Engineering
Background
- Adoptive T cell therapy shows promise for cancer treatment but carries risks of off-tumor effects.
- Noninvasive tracking methods are crucial for monitoring engineered cell behavior and ensuring safety in clinical applications.
- Human deoxycytidine kinase triple mutant (hdCK3mut) is a PET reporter previously validated for tracking hematopoiesis.
Purpose Of The Study
- To engineer and evaluate a novel PET reporter system for tracking anti-melanoma T cells in immunotherapy models.
- To assess the ability of hdCK3mut to monitor T cell engraftment, tumor homing, and function without compromising therapeutic efficacy.
Main Methods
- Engineered a construct for coexpression of hdCK3mut and the F5 anti-melanoma T cell receptor.
- Introduced the construct into human CD34 cells and peripheral blood mononuclear cells (PBMCs).
- Evaluated T cell tracking, tumor homing, and anti-tumor activity in preclinical immunotherapy models using [18F]-L-FMAU PET imaging.
Main Results
- hdCK3mut expression allowed visualization of engrafted cells in bone marrow and detection of intratumoral T cell homing.
- T cells coexpressing hdCK3mut and the T cell receptor showed enhanced signals in matched tumors.
- Engineered T cells demonstrated potent anti-tumor cytotoxicity, IFN-γ production, and activation, with no observed impact on T cell function.
Conclusions
- hdCK3mut reporter imaging provides a sensitive, noninvasive method for simultaneous monitoring of T cell engraftment and tumor infiltration.
- This approach holds significant potential for clinical translation in adoptive cell therapies, enhancing safety and efficacy monitoring.