Methods for inhibiting HIV or HCV infection by administering TIM-3 binding inhibitors
Inventors
Jones, Richard B. • Ostrowski, Mario • Nixon, Douglas F. • Ndhlovu, Lishomwa C. • Rini, James
Assignees
University of California San Francisco UCSF • University of California San Diego UCSD • Immunitybio Inc
Publication Number
US-11261231-B2
Publication Date
2022-03-01
Expiration Date
2028-10-27
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Abstract
The application relates to methods of treating chronic viral infection by modulating Tim-3 activity. In addition, the present application relates to methods of diagnosing or monitoring immune system activity or function, chronic viral infection and inflammatory disease using Tim-3 expression.
Core Innovation
The invention provides methods for treating chronic viral infection by modulating Tim-3 activity. Specifically, the inventors have discovered a population of functionally impaired T cells in subjects infected with acute and chronic viruses, such as HIV, that express the glycoprotein Tim-3 on their surface. Blocking Tim-3 activity was shown to improve immune system function, notably restoring T-cell functionality.
The problem addressed in the application is the inability of the immune system to control chronic viral infections such as HIV-1 and HCV, which is related to the functional impairment or exhaustion of virus-specific CD8+ and CD4+ T cells. This exhaustion manifests as a loss of proliferative capacity, cytotoxic potential, and cytokine production, leading to disease progression and eventual immune system failure.
The core innovation includes methods for diagnosing, monitoring, and treating immune system activity, chronic viral infection, and inflammatory disease through the assessment and modulation of Tim-3 expression on T cells. This encompasses administering Tim-3 inhibitors to subjects with viral infections, using Tim-3 expression as a biomarker for immune dysfunction, and co-administering Tim-3 inhibitors with antigens to induce or enhance immune responses. The invention also covers compositions comprising soluble forms of Tim-3 and various approaches to inhibit Tim-3 function via antibodies, peptides, or nucleic acids.
Claims Coverage
There is one independent claim, which represents a primary inventive feature.
Inhibition of HIV or HCV infection by administering a Tim-3 binding inhibitor
A method for inhibiting a viral infection in a subject, where the method comprises: - Administering an effective amount of an inhibitor of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3). - The inhibitor must be a means for binding Tim-3. - The viral infection to be treated is human immunodeficiency virus (HIV) infection or hepatitis C virus (HCV) infection. - The Tim-3 targeted by the inhibitor must have at least 90% sequence identity to SEQ ID NO: 2 or 6. - The inhibitor can include, but is not limited to, anti-Tim-3 antibodies that specifically bind to an amino acid sequence according to SEQ ID NO: 2 or 6. - The method can further include administering an effective amount of an antigen expressed by a virus that causes a chronic infection. - The chronic virus can be HIV-1 or HCV.
The independent claim defines the use of Tim-3 binding inhibitors, including specific antibodies, for the treatment of HIV or HCV infection, with further possible inclusion of viral antigens for chronic viral infections.
Stated Advantages
Blocking Tim-3 activity improves immune system function by enhancing T cell proliferation and cytokine production.
Tim-3 inhibition can restore the function of functionally impaired T cells in subjects with chronic or acute viral infection.
The methods allow for monitoring immune system activity, viral load, disease progression, or therapy efficacy through measurement of Tim-3 expression on T cells.
Administering an inhibitor of Tim-3 may reverse immune defects that persist even with antiretroviral therapy such as HAART.
Co-administration of a Tim-3 inhibitor with a viral antigen can induce or enhance an immune response against chronic viruses.
Documented Applications
Treatment of subjects afflicted with human immunodeficiency virus (HIV) infection or hepatitis C virus (HCV) infection by administration of a Tim-3 binding inhibitor.
Monitoring and assessing immune system activity or function in subjects by determining Tim-3 expression on T cells.
Diagnosing or monitoring chronic or acute viral infection and inflammatory disease using Tim-3 expression as a biomarker.
Monitoring or assessing viral load and disease progression in subjects with viral infection by comparing Tim-3 expression to a control.
Monitoring the efficacy of highly active antiretroviral therapy (HAART) by determining changes in Tim-3 expression on T cells.
Reversing immune defects persisting with HAART therapy by administering a Tim-3 inhibitor.
Improving or restoring the function of functionally impaired T cells by treating with a Tim-3 inhibitor.
Inducing an immune response in a subject against a chronic virus, including HIV-1 or HCV, by co-administering a viral antigen and a Tim-3 inhibitor.
Treating or preventing a chronic viral infection in a subject by co-administering an effective amount of a chronic viral antigen and an inhibitor of Tim-3.
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