Real-time monitoring of nanobubble-labeled chimeric antigen receptor t cell trafficking via contrast-enhanced ultrasound

The National Cancer Institute awarded Case Western Reserve University $100,228 on December 1, 2026, under the Cancer Research Manpower program (CFDA 93.398) to develop real-time monitoring of nanobubble-labeled chimeric antigen receptor T cell trafficking via contrast-enhanced ultrasound imaging.

The award funds research to refine nanobubble labeling protocols for prostate-specific membrane antigen (PSMA)-targeting CAR-T cells, enhancing imaging duration and stability to enable extended monitoring in both in vitro and in vivo settings. The first research aim optimizes nanobubble labeling techniques to achieve prolonged imaging timeframes for robust and sustained visualization of PSMA CAR-T cells. The second aim assesses CAR-T cell biodistribution, localization, and persistence in vivo using contrast-enhanced ultrasound in both tumor-bearing and non-tumor-bearing mice. The research addresses gaps in real-time monitoring of CAR-T cell behavior and distribution in solid tumor applications, with findings intended to support personalized dosing and treatment strategies and advance cancer immunotherapy and therapeutic monitoring applications.

The recipient is Case Western Reserve University's Office of Research Administration, operating in affiliation with University Hospitals of Cleveland. Work is performed in Cleveland, Ohio. The period of performance runs from December 1, 2026, through June 30, 2028. The assistance type is a project grant.

Abstract

The clinical impact of car-t cell-based immunotherapy is clear, with multiple FDA-approved treatments now available for acute lymphoblastic leukemia (all), b cell and follicular lymphomas, and multiple myeloma. Building on this success, significant efforts are focused on developing car-t cell therapies for solid tumors. However, limitations in real-time monitoring of car-t cell behavior and distribution make IT challenging to comprehensively assess their efficacy and safety. We hypothesize that nanobubble-based ultrasound contrast agents can reliably label prostate-specific membrane antigen (psma)- targeting car-t cells, enabling real-time visualization in vivo. Our preliminary data shows that nanobubbles (NBS), which are ultrasound contrast agents with a lipid shell surrounding a C4F10 gas core and diameters of 200-400 NM, can be effectively internalized by car-t cells. This allows for direct labeling and visualization using nonlinear contrast-enhanced ultrasound (ceus). The goal of this proposal is to refine our labeling protocol to enhance imaging duration and stability, enabling extended psma car-t cell monitoring in both in vitro and in vivo settings. Our first aim is to optimize nanobubble labeling techniques to achieve prolonged imaging timeframes, ensuring robust and sustained visualization of psma car-t cells. The second aim focuses on assessing car-t cell biodistribution, localization, and persistence in vivo using ceus in both tumor-bearing and non-tumor-bearing mice. This approach will provide crucial insights into car-t cell behavior within solid tumors. The findings have the potential to advance real-time car-t cell monitoring, supporting personalized dosing and treatment strategies, and contributing broadly to cancer immunotherapy, BIO-imaging, and therapeutic monitoring applications.