Project Funding Details


Title
Translating monoclonal antibody pharmacokinetics into clinical practice: toward personalized immunotherapy
Alt. Award Code
2025-30591-16876
Funding Organization
Fondazione AIRC
Budget Dates
2025-01-02 to 2026-04-01
Principal Investigator
Idili, Andrea ORCiD Logo 000000026004270X
(ORCiD iD)
Institution
Università degli Studi di Roma "Tor Vergata" (University of Rome Tor Vergata)
Region
Europe & Central Asia
Location
Roma, IT

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Technical Abstract

Monoclonal antibodies (mAbs) have revolutionized cancer therapy, but their efficacy is limited by significant inter-individual variability in patient response. This variability, influenced by tumor heterogeneity, immune response, and patient characteristics, leads to unpredictable pharmacokinetics and forces clinicians to administer high doses of mAbs, increasing treatment costs. Monitoring mAb concentrations in patients could enable personalized dosing, but current bioanalytical methods are complex, costly, and unsuitable for point-of-care use, hindering their implementation in clinical practice. As a result, the variability of mAbs remains poorly understood, hampering personalized immunotherapy. Imagine a future where monitoring life-saving immunotherapy drugs is as easy as testing your blood sugar at home. We hypothesize that a point-of-care device capable of rapidly and accurately measuring mAb levels could revolutionize cancer treatment by providing patients and physicians with real-time, personalized data. This innovative tool would not only simplify monitoring, but also enable tailored dosing adjustments, optimize therapeutic decisions and ultimately improve patient outcomes. In addition, by simultaneously tracking anti-drug antibodies (ADA) and total IgG, this device could provide critical insight into the factors that influence treatment response, paving the way for a new era of precision medicine in oncology. Leveraging my expertise in DNA nanotechnology, in vivo biosensing, and point-of-care (PoC) platforms, I propose a groundbreaking approach to develop a biomedical device for monitoring clinically relevant antibodies (mAbs, ADA, IgG). The overarching goal of my research program is to create a rapid (< 15 min), single-step, affordable, and versatile biosensing technology capable of quantifying multiple antibodies in a finger-prick blood sample directly at the point-of-care. Specifically, I will focus on the quantification of therapeutic mAbs (trastuzumab, bevacizumab, rituximab), their associated anti-drug antibodies (ADA), and human IgG. This will be achieved by harnessing the adaptability and programmability of DNA in conjunction with the advantages of electrochemical platforms to develop innovative electrochemical DNA-based (eDNA) sensors. This research aims to revolutionize immunotherapy by developing a portable, low-cost device capable of rapidly detecting mAbs, ADA, and total IgG directly in blood. This will be achieved through the creation of programmable eDNA sensors, utilizing aptamers and DNA scaffolds as recognition elements for specific antibody detection. These sensors will be engineered with allosteric mechanisms to finely tune their sensitivity, enabling precise monitoring of antibody concentrations across a broad therapeutic range. The integrated platform will combine these sensors with a miniaturized electrochemical device and open-source software, paving the way for personalized immunotherapy and enhanced patient care. This research aims to revolutionize immunotherapy by developing a PoC eDNA sensor platform enabling personalized treatment through rapid, multiplexed antibody detection and quantification, direct measurement of pharmacologically active drug fractions, and real-time monitoring. This research will yield an innovative biomedical device enabling personalized immunotherapy. The device will allow for real-time monitoring of therapeutic antibodies, anti-drug antibodies, and total IgG, offering unprecedented insights into patient responses and treatment efficacy. This will empower clinicians to tailor dosing regimens, predict adverse reactions, and improve treatment selection, ultimately enhancing the cost-effectiveness of immunotherapy and making it more accessible to patients.

Cancer Types

  • Not Site-Specific Cancer

Common Scientific Outline (CSO) Research Areas

  • 4.2 Early Detection, Diagnosis, and Prognosis Technology and/or Marker Evaluation - Fundamental Parameters
  • 4.3 Early Detection, Diagnosis, and Prognosis Technology and/or Marker Testing in a Clinical Setting