BACKGROUND:
PML is a demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV) occurring in immunocompromised patients that is usually progressive and often fatal. There are no currently available treatment options and high unmet medical need. Previous data has indicated that JCPyV- or BK polyomavirus-specific T cell products could be a promising treatment strategy for PML. We aimed to optimize and develop 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 JCPyV-specific platform derived from LT, ST, VP1, VP2 and VP3 antigens of JCPyV covering 35 class I and class II HLA alleles.
DESIGN/METHODS:
CE-VST01-JC drug product was manufactured by expanding JCPyV-specific T cells from healthy donors using the HLA-defined peptide mix for 17 days in culture media supplemented with IL-2 in GRex bioreactors. CS-VST01-JC T cell product was further extensively assessed for JCPyV-specificity, allogenicity, functional and phenotypic characterization using flow cytometry.
RESULTS:
CE-VST01-JC immunotherapy was manufactured by stimulating antigen-specific T cells with a panel of HLA class I and class II-restricted peptide epitopes. 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.
CONCLUSIONS:
We have developed a robust manufacturing process for CE-VST01-JC adoptive T cell therapy which includes highly potent JCPyV-specific T cells with stem-cell like memory T cells, with no detectable off-target reactivity. Clinical safety and efficacy of CE-VST01-JC will be evaluated with a large 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’ (NCT#05541549) .