Tumor lysing genetically engineered T cells loaded with multi-modal imaging agents.

Area of Science:

• Biomedical Engineering
• Immunotherapy
• Medical Imaging

Background:

• Adoptively transferred T cells engineered with chimeric antigen receptors (CAR) show promise in cancer treatment by targeting tumor-associated antigens (TAA).
• Accurate imaging of CAR T-cell biodistribution is essential for optimizing therapeutic efficacy and patient safety, ensuring cells reach the tumor site and enabling precise dose management.

Purpose of the Study:

• To develop an efficient, non-toxic, and potentially cGMP-compliant method for loading T cells with multi-modal imaging contrast agents.
• To enable sensitive detection and high-resolution anatomical correlation of CAR T-cell accumulation at tumor sites.

Main Methods:

• Genetically modified T cells to express chimeric antigen receptors (CAR).
• Developed a process for loading T cells with Super Paramagnetic Iron Oxide Nanoparticles conjugated with Copper-64 (SPION-(64)Cu) for multi-modal PET-MRI imaging.
• Evaluated the in vitro targeting capability of CD19-specific CAR(+)SPION(pos) T cells against CD19(+) lymphoma models.

Main Results:

• Successfully developed a method for loading high numbers of T cells with SPION-(64)Cu, suitable for PET-MRI imaging.
• Demonstrated that (64)Cu-based PET can detect T cell accumulation with high sensitivity.
• Showcased that SPION-based MRI provides high-resolution, anatomically correlated images of T cell distribution.
• Confirmed effective in vitro targeting of CD19(+) lymphoma by CD19-specific-CAR(+)SPION(pos) T cells.

Conclusions:

• The developed SPION-(64)Cu loading process offers a viable strategy for tracking CAR T-cell biodistribution using combined PET-MRI.
• This multi-modal imaging approach can enhance the monitoring of CAR T-cell therapy, improving treatment outcomes and safety.