Up to 10% of transplanted patients develop a PTLD, Post-transplant lymphoproliferative disorder. This aggressive tumour arises as a result of reactivation of Epstein-Barr virus in a context of immunodepression.
PTLD screening currently involves systematic qPCR testing to detect an increase in Epstein-Barr viral load (EBV). All transplanted patients are screened continuously throughout their lifetimes, at first frequently, and then less frequently over the years if initial results are negative. False-positive and false-negative results have been reported with the qPCR test; it is also incompatible with early diagnosis.
ZETAQUANTOR offers an alternative for PTLD testing, applicable both for screening purposes and for early diagnosis.
The ZETAQUANTOR test quantifies the key EBV circulating viral protein associated with its lytic cycle – ZEBRA protein – as an indicator of activation of EBV replication. ZEBRA is a toxoid protein involved in tumour progression.
This innovative and simple diagnostic/screening method precisely measures early activation of replication of the EBV virus and thus provides more precise monitoring of PTLD development in transplant patients than the current reference method. The specificity and response time for ZETAQUANTOR are also better than those of the qPCR method.
The prototype of ZETAQUANTOR for diagnostic, prognostic, and therapeutic monitoring for PTLD measures the soluble ZEBRA protein either based on results from an antibody-based ELISA or lateral flow test.
– Protein markers are more reliable than molecular markers, offering up to 80% predictivity. The improvement compared to the current standard is particularly marked for HSC transplant patients
– The low cost and simplicity of implementation will facilitate transfer to clinical laboratories
– Early detection of ZEBRA will allow physicians to adapt the treatment offered to transplant patients by modulating immunosuppressive dose and/or initiating pre-emptive anti-CD20 treatment to directly target tumour cells.
A prototype test, using patented antibodies, is available. Threshold values for the test were established based on a retrospective study using over 400 samples from 66 transplant patients compared to samples from a population of asymptomatic non-transplant patients.
A new multi-center retrospective cohort study is underway to confirm these initial results. The secondary objective of this study is to determine whether the potential of the ZEBRA test could also be exploited in screening for other EBV-linked HSC complications. ZETAQUANTOR is currently seeking an in-licensing opportunity.
ZETAQUANTOR has the potential to systematically exploit ZEBRA as a new biomarker to monitor the PTLD status of patients following solid organ transplant (>150,000 patients/yr worldwide) or bone marrow transplant (>400,000 patients/yr worldwide).