Antibody with Infinite Affinity for In Vivo Tracking of Genetically Engineered Lymphocytes.

Area of Science:

• Immunology
• Biotechnology
• Medical Imaging

Background:

• Chimeric antigen receptor (CAR) T-cell therapy requires noninvasive methods to monitor T-cell biodistribution, viability, and function.
• Current tracking methods for CAR T cells are limited, hindering effective therapeutic assessment and management.

Purpose of the Study:

• To investigate the potential of DOTA antibody reporter 1 (DAbR1) as a reporter gene for noninvasive in vivo tracking of T cells.
• To evaluate DAbR1's utility for imaging CAR T cells and its potential as a suicide gene for managing immune-related adverse effects.

Main Methods:

• DAbR1 and green fluorescent protein were cloned into an SFG-retroviral vector for T-cell transduction.
• Cell surface expression of DAbR1 was confirmed using radiolabeled (S)-2-(4-acrylamidobenzyl)-DOTA (AABD).
• In vivo imaging feasibility and radiation doses were assessed using 86Y/177Lu-AABD in T cells and CAR T cells.

Main Results:

• DAbR1-expressing T cells showed significantly higher uptake of 86Y-AABD compared to control cells.
• In vivo imaging demonstrated successful tracking of DAbR1-positive CAR T cells with favorable biodistribution and image contrast.
• Selective T-cell ablation using 177Lu-AABD was shown to be feasible for clustered T-cell populations.

Conclusions:

• T cells can be successfully modified with DAbR1 for noninvasive in vivo tracking via PET and SPECT imaging.
• DAbR1 serves as a promising reporter gene for monitoring CAR T-cell therapy.
• The DAbR1 system holds potential for both therapeutic monitoring and managing adverse events in CAR T-cell therapy.