Abstract
A point-of-care blood test for the detection of an emerging biomarker, CCL17/TARC, could prove transformative for the clinical management of classic Hodgkin lymphoma (cHL). Primary care diagnosis is challenging due to nonspecific clinical presentation and lack of a diagnostic test, leading to significant diagnostic delays. Treatment monitoring encounters false-positive and negative results, leading to avoidable chemotherapy toxicity, or undertreatment, impacting patient morbidity and mortality. Here, we present an amperometric CCL17/TARC immunosensor, based on the utilization of a thiolated heterobifunctional cross-linker and sandwich antibody assay, to facilitate novel primary care triage and chemotherapy monitoring strategies for cHL. The immunosensor shows excellent analytical performance for clinical testing; linearity (R2 = 0.986), detection limit (194 pg/mL), and lower and upper limits of quantitation (387-50 000 pg/mL). The biosensor differentiated all 42 newly diagnosed cHL patients from healthy volunteers, based on serum CCL17/TARC concentration, using blood samples collected prior to treatment intervention. The immunosensor also discriminated between paired blood samples of all seven cHL patients, respectively, collected prior to treatment and during chemotherapy, attributed to the decrease in serum CCL17/TARC concentration following chemotherapy response. Overall, we have shown, for the first time, the potential of an electrochemical CCL17/TARC biosensor for primary care triage and chemotherapy monitoring for cHL, which would have positive clinical and psychosocial implications for patients, while streamlining current healthcare pathways.
Highlights
A point-of-care blood test for the detection of an emerging biomarker, CCL17/TARC, could prove transformative for the clinical management of classic Hodgkin lymphoma
CCL17/TARC is highly expressed by Hodgkin and Reed-Sternberg cells and most likely plays a role in attracting T helper 2 (Th2) cells into the tumor microenvironment.[1,2]
Pre- and on-treatment classic Hodgkin lymphoma (cHL) patient samples were collected from two studies: Investigation of The Cause of Hodgkin lymphoma (ITCH) and Biomarkers and classical Hodgkin lymphoma (BACH)
Summary
A point-of-care blood test for the detection of an emerging biomarker, CCL17/TARC, could prove transformative for the clinical management of classic Hodgkin lymphoma (cHL). A n electrochemical CCL17/TARC immunosensor for primary care triage and secondary care chemotherapy monitoring would represent a paradigm shift in the clinical management of classic Hodgkin lymphoma (cHL). CCL17/TARC is highly expressed by Hodgkin and Reed-Sternberg cells and most likely plays a role in attracting T helper 2 (Th2) cells into the tumor microenvironment.[1,2] CCL17/TARC is elevated in ≥90% of untreated cHL patient serum samples relative to healthy persons,[3,4] and correlates with tumor burden,[4−6] and Ann Arbor stage.[3,5,7,8] CCL17/TARC falls rapidly in response to successful treatment.[4]. Itchy skin and alcohol-induced lymph node pain may be present.[14−16]
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