CE-VST01-JC: a Novel Allogeneic T-cell Based Immunotherapy for the Treatment of Progressive Multifocal Leukoencephalopathy (PML)
George Ambalathingal1, Sadie Whittaker2, Derrell Porter2, Irene Cortese3, Rajiv Khanna1
1QIMR, 2Cellevolve Bio, 3Experimental Immunotherapeutics Unit, National Institute of Neurological Disorders and Stroke, NIH
To develop a novel, allogenic T cell-based immunotherapy for the treatment of PML.

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.

Pubished data has indicated that JCPyV- or BK polyomavirus-specific T cell products could be a promising treatment strategy.

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.