Towards Precision CAR T-cell Immunotherapy: extended gate FET biosensor for personalized drug monitoring

Selection and optimization of therapies for cancer patients urgently needs personalization. Portable point-of-care electronic biosensors emerge as a groundbreaking solution to contribute to better decision-making in precision oncology. This study showcases the innovative use of extended gate field-effect transistor (EG-FET) biosensors to monitor the concentration and pharmacokinetics of immunotherapeutic drugs in vivo. Complementary positron emission tomography (PET) and radioactivity biodistribution studies in mice validate the EG-FET measurements. We introduce a novel indirect assay format for detecting target modules in an adapter CAR T-cell therapy model, effectively addressing the limitations of traditional potentiometric measurements. The EG-FET sensors exhibit exceptional sensitivity, and fulfill the requirements for immunotherapeutic drug monitoring without the need for complex radioactive labeling. In pharmacokinetic evaluations, the FET-based biosensor's performance aligns with standard radioactive measurements, revealing the distinct lifespans of small-sized TMs (15 minutes for scFv type) and larger TMs (14 hours for IgG4 type). These promising findings advocate for further exploration of next-generation biosensors in therapeutic monitoring roles. With their cost, size, and response time advantages, these biosensors hold immense potential for advancing personalized oncology, transcending the conventional diagnostic roles typically highlighted in the literature.