A Novel Method for Detecting Lytic Human Herpesvirus 6 in T cell Therapies to Identify Patients at Risk of Encephalitis and Enable Safety Screening of T cell Products

Stanford scientists have developed a method to detect reactivated human herpesvirus 6 (HHV-6) in T cell therapies using genomics technologies, including single-cell sequencing. Detecting lytic herpesvirus 6 in T cell therapies can identify patients at risk of encephalitis and assist in ensuring the safety of T cell products.

Cell therapies have yielded durable clinical benefits for patients with cancer but have been accompanied by unexpected side effects. For instance, approximately 1 in 40-100 patients who undergo CAR T cell therapy suffer from HHV-6 encephalitis. Unexpectedly, the source of the lytic HHV-6 virus can come from the cell therapy itself. Therefore, the detection of lytic HHV-6 in T cell therapies can serve as a diagnostic tool to identify patients at risk of encephalitis and as a safety screening method for T cell products.

Using single-cell sequencing, a rare polyclonal population of HHV-6 'super-expressors' (~1 in 360-10,000 cells) that possess high viral transcription and lytic activity late in chimeric antigen receptor (CAR) T cell culture were identified in vitro. Further, through the reanalysis of single-cell sequencing data from FDA-approved cell therapy products, the presence of CAR+, HHV-6+ super-expressor T cells were detected in vivo. Together, this implicates the T cell therapy as a potential source of lytic HHV-6 reported in multiple clinical trials and has broad implications for the design, screening, and diagnosis of unexpected toxicities in cell therapies.

Stage of Development:
Preclinical – in-vivo data