Toward Personalized Immunotherapeutic Drug Monitoring with Multiplexed Extended-Gate Field-Effect-Transistor...

Area of Science:

• Biomedical Engineering
• Oncology
• Biosensor Technology

Background:

• Personalized cancer therapy requires precise monitoring of drug concentrations and pharmacokinetics.
• Existing monitoring methods often lack the sensitivity, speed, or non-invasiveness needed for real-time clinical decisions.
• Electronic biosensors offer a promising avenue for point-of-care therapeutic drug monitoring.

Purpose of the Study:

• To demonstrate the utility of extended-gate field-effect-transistor (EG-FET) biosensors for in vivo monitoring of immunotherapeutic drugs.
• To introduce a novel indirect assay for detecting target modules in CAR T-cell therapy.
• To validate EG-FET measurements using complementary positron emission tomography and biodistribution studies.

Main Methods:

• Development and application of EG-FET biosensors for real-time monitoring of immunotherapeutic drugs in vivo.
• Utilized positron emission tomography and radioactivity biodistribution studies for validation.
• Introduced a novel indirect assay format for detecting target modules in a chimeric antigen receptor T-cell therapy model.

Main Results:

• EG-FET biosensor performance closely matched standard radioactivity measurements in pharmacokinetic evaluations.
• Distinct lifespans were determined for small (15 min) and large (14 h) target modules.
• Demonstrated exceptional sensitivity and eliminated the need for radioactive labeling in immunotherapeutic drug monitoring.

Conclusions:

• EG-FET biosensors are highly effective for in vivo monitoring of immunotherapeutic drugs, aligning with established methods.
• The novel indirect assay addresses limitations in potentiometric measurements for target module detection.
• Next-generation electronic biosensors, like EG-FETs, show significant potential for advancing personalized oncology due to their cost, size, and speed advantages.