Antigen-Specific T Cell Receptor Discovery For Treating Progressive Multifocal Leukoencephalopathy

Patent Status

Patent Pending

Brief Description

Progressive Multifocal Leukoencephalopathy (PML) is a devastating and often fatal demyelinating disease of the central nervous system caused by the reactivation of the JC virus (JCV). In immunocompromised patients, the absence of effective T cell surveillance allows the virus to infect and lyse oligodendrocytes, leading to irreversible neurological damage. UC Berkeley researchers have developed a method for discovering and engineering antigen-specific T cell receptors (TCRs) that specifically target JCV.

Suggested uses

• Adoptive Immunotherapy: Direct treatment for patients suffering from PML to halt viral replication and disease progression.

• Prophylactic Treatment: Use in high-risk immunocompromised individuals, such as those undergoing specific monoclonal antibody therapies (e.g., natalizumab), to prevent JCV reactivation.

• Off-the-Shelf Cell Bank: Developing a library of TCR-engineered T cells covering diverse HLA haplotypes for rapid clinical deployment.

• Combination Therapy: Use alongside immune reconstitution therapies to accelerate the clearance of JCV from the central nervous system.

• Diagnostic Research: Utilizing identified JCV-specific TCR sequences as biomarkers to monitor patient immune status and risk of PML.

Advantages

• Target Specificity: Engineered TCRs are precisely tuned to JCV epitopes, minimizing off-target effects and potential autoimmunity.

• Potent Cytotoxicity: Modified T cells demonstrate high-avidity binding and efficient killing of JCV-infected astrocytes and oligodendrocytes.

• Rapid Deployment: Provides an immediate therapeutic option for patients who cannot wait for the lengthy expansion of autologous virus-specific T cells.

• Broad Applicability: Discovery platform can be scaled to identify TCRs for various HLA subtypes, ensuring a wider patient reach.

• Overcomes Immunosuppression: Bypasses the patient's compromised immune system by providing "pre-programmed" functional T cell immunity.

Related Materials