Monitoring Persistence of CAR T Cells via Non-invasive Imaging

Using this approach, clinicians will be able to obtain valuable data to help guide therapeutic decisions.

Diagnostics

Project Overview

Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized the treatment of a spectrum of blood-borne malignancies.
There is a clinical need for transformative imaging approaches that can provide real-time feedback on CAR T cell activity, persistence and location.
Dana-Farber researchers have developed a non-invasive imaging platform for real-time in vivo monitoring of the persistence and location of CAR T cells.
Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing this asset for further development into new CAR imaging techniques.

Technology

Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized the treatment of a spectrum of blood-borne malignancies. Many different antigens presented on tumor cells can be targeted by CAR T cells. Currently, two therapies, targeting CD19 and BCMA, have been FDA-approved with new therapies expected to follow. The success of CAR T cell therapy relies on multiple factors including the persistence of CAR T cells post-administration and their ability to target tumor cells presenting the targeted antigen. Monitoring these processes is currently limited to elaborate blood tests to assess cytokine concentration, dPCR analysis, or direct CAR T cell interrogation using flow cytometry. However, these methods do not provide information on spatial distribution of infused CAR T cells and do not accurately represent or quantify the extent of CAR T cell expansion and their tumor infiltration.

Alternatively, non-invasive imaging of CAR T cells can be performed through in vivo labeling of CAR T cells after infusion using a small molecule PET tracer specific for a reporter gene that is coexpressed with the CAR construct. Although attractive, this approach has seen limited clinical use since it does not provide information on the spatial distribution of the infused CAR T cells. Also, blood analyses may not accurately quantify the extent of CAR T cell tumor infiltration and expansion. Therefore, there is a clinical need for transformative imaging approaches that can provide real-time feedback on CAR T cell activity, persistence and location

To address this unmet need, Dr. Rashidian and his lab at the Dana-Farber Cancer Institute have developed a non-invasive imaging platform for real-time in vivo monitoring of the persistence and location of CAR T cells. The protein-based platform is comprised of an antigen, targeted by the CAR T cell (e.g. CD19 or BCMA), and a PET tracer. Using the approach, clinicians will be able to obtain valuable CAR T efficacy and persistence data to help guide therapeutic decisions.

Further details:

Julia Fröse et al ,Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool. Science Advances. 10:38(2024)

Benefits:

No additional genetic modifications of CAR T cells needed.
Non-invasive.
High sensitivity and selectivity.
Constructs are comprised of human self-proteins to avoid any immunogenicity.
Can be used in combination with any CAR T cell therapy.

Team Members: Mohammad Rashidian, PhD, Taha Rakhshandehroo, PhD, Michael T. Hemann, PhD, Julia Froese, PhD

Applications

Clinical patient care: Inform clinical decision making, such as deciding when to administer additional doses of CAR therapy or initiate a combination therapy.
Help identify potential safety issues associated with CAR therapy such as off-target effects or immune-mediated toxicities.
Enable early assessment of CAR T cell engraftment and persistence allowing for prediction of a potential relapse or adjustments in treatment if necessary.

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing this asset for further development into new CAR imaging techniques.

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