PML is a demyelinating disease of the CNS caused by JC polyomavirus (JCPyV) occurring in immunocompromised patients. It is progressive and often fatal. There are no treatment options.

We have developed a novel allogeneic T cell-based immunotherapy, CE-VST01-JC, which consists of JCPyV‑specific T cells expanded using a targeted, highly curated mixture of 36 JCPyV-specific peptides derived from LT,ST, VP1, VP2 and VP3 antigens of JCPyV covering 35 class I and class II HLA alleles. The peptide mixture is designed to result in a drug product that has high specificity and more immunogenic precision, while minimizing the risk of GvHD. 

 CE-VST01-JC was manufactured by expanding JCPyV-specific T cells from healthy donors using the HLA-defined peptide mix, then extensively assessed for JCPyV-specificity, allogenicity, functional and phenotypic characterization.

In vitro characterization of CE-VST01-JC indicates a highly potent drug product of JCPyV -specific T cells with stem-cell like memory T-cells and no detectable off-target reactivity. 

These T cells displayed polyfunctional profile with co-expression of IFN γ, TNF and IL-2. Phenotypic characterization of these T cells also showed enrichment of stem-cell like memory T cells (CD95, CD62L and CXCR3 co-expression) along with effector memory cells. Further allogenicity assessment against 115 HLA-alleles showed no alloreactive T cells in CE-VST01-JC immunotherapy.

Clinical safety and efficacy will be evaluated with a global study, entitled: ‘ASCEND-JC: A Multi-center, Randomized, Double-blind, Phase 2 Study, Evaluating JCPyV-specific T cell therapy for the Treatment of PML’ beginning early 2023. This will be the largest PML study conducted and has potential to provide clinical validation for an allogenic virus specific T-cell platform for the treatment of a disease with high unmet need.