NewYork-Presbyterian/Columbia University Medical Center

Author Of 1 Presentation

Disease Modifying Therapies – Risk Management Poster Presentation

P0282 - Advancing antigen-specific T cell therapy for progressive multifocal leukoencephalopathy (ID 1896)

Speakers
Presentation Number
P0282
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Progressive multifocal leukoencephalopathy (PML) is an often fatal white matter disease caused by the polyomavirus JC virus that affects patients with various types of immunodeficiencies. Some multiple sclerosis disease modifying therapies, including natalizumab, dimethyl fumarate and fingolimod, increase the risk for PML. Successful PML treatment and survival is critically dependent on early recognition and immune reconstitution; unfortunately, rapid immune reconstitution is not always achievable. New therapies are being investigated, including a pilot study conducted at NIH exploring ex vivo T cells generated from polyomavirus-specific partially matched first degree relative donors of PML patients (NCT02694783). Anti-viral specific cell products were generated following 14-day culture with 15mer polyomavirus peptide libraries.

Objectives

To perform T cell immune repertoire sequencing on donor polyomavirus-specific T cell populations with the goal of identifying T cell receptors (TCRs) that might be used to create a new “off the shelf” designer T cell therapy for PML.

Methods

T cells from twelve first degree relative donors and four PML patients from the NIH study were obtained, including donor T cells pre- and post-polyomavirus antigen stimulation. Using immune repertoire sequencing of CD4 and CD8 T cells, V(D)J sequences from post-stimulation donor cells were analyzed to identify clonally expanded TCRs relative to the pre-stimulation, same donor controls. Clonally expanded TCRs were also compared to PML patient V(D)J sequences to look for sequence similarity. Once candidate TCRs are identified, we will perform functional assays to determine their effectiveness against JC virus-infected cells.

Results

Candidate TCRs and their antigen specificity will be presented at the meeting in the hopes that the most effective candidate TCRs can serve as therapeutics for HLA-matched patients with PML.

Conclusions

Candidate TCRs and their antigen specificity will be presented at the meeting in the hopes that the most effective candidate TCRs can serve as therapeutics for HLA-matched patients with PML.

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