Directly Isolated Allogeneic Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy

Area of Science:

• Immunology
• Virology
• Neurology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a severe, life-threatening viral infection.
• Currently, there is no approved antiviral treatment for PML, highlighting an unmet medical need.

Purpose of the Study:

• To evaluate the therapeutic potential of directly isolated allogeneic virus-specific (DIAVIS) T cells in restoring immune function in PML patients.
• To assess the efficacy of DIAVIS T-cell therapy as a treatment option when other curative strategies are unavailable.

Main Methods:

• A retrospective case series involving 28 PML patients treated between March 2020 and February 2022.
• DIAVIS T cells, isolated from healthy donors and targeted against BK polyomavirus, were administered to patients.
• Outcomes were compared to a historical control group receiving best supportive treatment (BST) and to real-world data of patients treated with immune checkpoint inhibition.

Main Results:

• Twenty-two of 28 patients (79%) showed a clinical response, with stabilization or improvement and reduced viral load.
• Survival analysis indicated significantly better 12-month survival rates for patients treated with DIAVIS T cells (69%) compared to historical BST controls (45%).
• Older age was identified as the sole predictor of a poor treatment response.

Conclusions:

• This case series provides Class IV evidence suggesting that DIAVIS T-cell therapy is effective in reducing mortality and improving functional outcomes in PML patients.
• Further prospective studies are necessary to validate these promising findings and confirm the efficacy of this therapeutic approach.