A Novel Enhanced Lateral Flow Assay (ELFA) Technology for Graft Immunomonitoring in Vascularized Composite Allotransplantation (VCA)
Abstract
Trauma is common in both military and civilian settings, and burns, amputation, and other non-salvageable tissue injuries can significantly impact form and function. Vascularized composite allotransplantation (VCA) involves transplants of multiple tissues such as muscle, bone, nerve, and skin as functional units. VCA can serve to replace lost or damaged tissue following a traumatic event and can have a significant impact on the restoration of form and function. VCA has gained increasing importance in clinical practice and may evolve into an important component of multidisciplinary approaches to reconstruction after severe injuries. To date, sources have reported as many as 150 upper-extremity and 40 face transplants performed worldwide. VCA such as hand or face transplants require lifelong immunosuppressant drugs so the transplant is not rejected. More importantly, it is critical to frequently monitor these drug levels, as well as levels of circulating inflammation biomarkers that have shown to be good predictors for early transplant rejection. Every transplant recipient absorbs and processes these drugs differently, and long-term use can cause other serious health issues. Key to a successful outcome in VCA recipients is frequent drug level monitoring to (1) identify transplant rejection early on and (2) ensure that immunosuppressant drug levels are neither too high nor too low. However, current methods for monitoring immunosuppressant drug levels require blood draws and laboratory processing and reporting, and early rejection biomarker measurements are isolated from tissue/skin biopsy samples, which contributes to infrequent monitoring and suboptimal drug peak and trough levels. To enable more frequent monitoring of VCA transplant recipients, there is a need for methods that are patient-friendly, reliable, and accurate in a diversity of care settings. The enhanced lateral flow assay technology developed by Intelligent Optical Systems (IOS) will combine measurements of immunosuppressant drug levels and early rejection biomarkers in an integrated, easy-to-use, lateral flow assay test platform that uses fingerstick sampling of whole blood, similar in format to a glucose meter. The technology builds on the rapid assay platform previously developed by IOS and represents the logical progression of their ongoing development of an immunosuppressant drug assay (tacrolimus) that has demonstrated therapeutic levels of detection in plasma with a high degree of reproducibility. The ease of use, low cost, and rapid analysis provided by this platform will add a novel clinical and ultimately home-based tool for VCA recipients (as well as solid organ [i.e., kidney] transplant recipients), enabling more frequent monitoring, thus improving outcomes by adjusting immunosuppressant drug dosage and mitigating rejection. The proposed technology represents a significant advancement to better enable monitoring and optimization of immunosuppressant drug levels, protocol adherence, and treatment progression. When combined with inflammation markers, this technology will help to both identify rejection episodes early and follow treatment to limit rejection and toxicity. Improving adherence and optimizing existing immunosuppressant drug protocols is a near-term goal that we believe can be impactful as a means to reduce long term toxicity of immunosuppression and improve the safety and efficacy of protocols.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110972
Entities
People
- Trong Nguyen
Organizations
- United States Army