A novel allogeneic T cell-based immunotherapy, CE-VST01-JC, for progressive focal leukoencephalopathy will be evaluated for clinical safety and efficacy.
Australian researchers have developed a novel allogeneic T cell-based immunotherapy, CE-VST01-JC, by expanding JC polyomavirus (JCPyV)-specific T cells from healthy donors. Clinical safety and efficacy will be evaluated in a global study called ASCEND-JC. If successful, this allogenic T cell-based immunotherapy could become the first available treatment for progressive focal leukoencephalopathy (PML).
PML is a very rare, devastating and often fatal demyelinating disease of the central nervous system caused by the JCPyV. Risk groups include those who are severely immunosuppressed, such as transplant recipients, patients with HIV, and those with MS on certain medications. The increasing use of immunosuppressive treatments in recent years has caused an increase in the prevalence of PML, for which there is currently no treatment.
George Ambalathingal, PhD, said T cell therapy has been highlighted as a promising approach for PML over the past decade, especially JCPyV- or BK polyomavirus (BKPyV)-specific T cell products. Dr. Ambalathingal’s group developed a novel, allogeneic, off-the-shelf T cell-based immunotherapy, CE-VST01-JC, which consists of JCPyV-specific T cells from healthy donors. The T-cells were expanded using a targeted, highly curated peptide mix, defined by human leukocyte antigens (HLA). According to Dr. Ambalathingal, this mixture consisted of 36 JCPyV-specific peptides derived from all 5 antigens of JCPyV: LT, ST, VP1, VP2 and VP3, covering 32 class 1 and class 2 HLA alleles. It has been extensively assessed for JCPyV-specificity and allogenicity and has been functionally and phenotypically characterized.
The result has high specificity and more immunogenic precision while also minimizing the risk of graft-versus-host disease. The in vitro characterization indicated that CE-VST01-JC contains highly potent JCPyV-specific T cells with stem-cell-like memory T cells, lacking any off-target reactivity.
Clinical safety and efficacy of CE-VST01-JC will be evaluated in the multi-center, randomized, double-blind, phase 2 ASCEND-JC study with an adaptive design. The trial was recently approved by the FDA and should start in late 2023 or early 2024. Up to 60 participants will be randomized 2:1 to four infusions of 100 million cells of HLA-matched JCPyV-specific T cells each or placebo. Dr. Ambalathingal said it will be the largest trial of a PML treatment ever. Meanwhile, both CE-VST01-JC and T cell treatment for the BK-virus (CE-VST01-BK) has been made available in Australia for compassionate use. The results in 12 participants were very promising and encouraging, according to Dr. Ambalathingal.
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