Long lived T cells for treating HIV infection
Inventors
Sekaly, Rafick-Pierre • Sharma, Ashish • ZEIDAN, JOUMANA
Assignees
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Publication Number
US-12698318-B2
Publication Date
2026-08-04
Expiration Date
Abstract
A method of treating an HIV infected subject includes administering the subject an enriched CCR5 and/or CXCR4 gene edited CD4+ T cell population characterized by intermediate cells surface co-expression of CD45A and CD450 (RAintROint).
Core Innovation
The invention relates to an isolated enriched CD4+ T cell population characterized by intermediate cell surface co-expression of CD45RA and CD45RO (CD45RAint CD45ROint) and expression of CD95+, CD127+, TCF7+ and CD27+. The cells are modified such that they are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor, and at least 50% of the enriched population has a CD45RAint CD45ROint CD95+CD127+CD27+ phenotype.
The invention further relates to separating and/or enriching isolated CD4 T cells into cells having a CD45RAint CD45ROint phenotype with increased expression of TCF7 compared to the isolated CD4 T cells prior to separation and/or enrichment. Enriching includes culturing with IL-7 and IL-15 to promote expansion and/or formation of the enriched population, with the IL-7 and IL-15 concentration being less than 10 ng/ml.
The described therapeutic concept includes using the enriched, gene-modified CD4+ T cell population in the context of antiretroviral therapy. The content links the CD45RAint CD45ROint marker profile to long-lived, stem-like/quiescent properties and to intended therapeutic outcomes after infusion into an HIV-infected subject.
Claims Coverage
The claims cover three inventive features: generating an enriched CD4 T cell population with CD45RAint CD45ROint and increased TCF7, modifying the cells to be devoid of functional CCR5 and/or CXCR4, and administering the enriched population to an HIV-infected subject. The claims also include an isolated enriched CD4+ T cell population with the specified marker profile and a composition requirement that at least 50% of the population has a CD45RAint CD45ROint CD95+CD127+CD27+ phenotype.
Enriched CD45RAint CD45ROint TCF7+ CD4 T cells
Separating and/or enriching isolated CD4 T cells into cells having a CD45RAint CD45ROint phenotype and increased expression of TCF7 compared to the isolated CD4 T cells prior to separation and/or enrichment, with at least 50% of the enriched population having a CD45RAint CD45ROint CD95+CD127+CD27+ phenotype.
IL-7 and IL-15 culture to promote expansion
Culturing isolated CD4 T cells with IL-7 and IL-15 effective to promote expansion and/or formation of an enriched population of CD4 T cells having the CD45RAint CD45ROint phenotype, wherein the IL-7 and IL-15 concentration is less than 10 ng/ml.
Modified to be devoid of functional CCR5 and/or CXCR4 co-receptor
Modifying the CD4 T cells such that the CD4 T cells are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor before separating and/or enriching, or modifying the separated and/or enriched CD45RAint CD45ROint phenotype CD4 T cells so that they are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor.
Isolated enriched CD4+ T cell population with specified markers
An isolated enriched CD4+ T cell population characterized by intermediate surface co-expression of CD45RA and CD45RO (CD45RAint CD45ROint) and expression of CD95+, CD127+, TCF7+ and CD27+, wherein the cells are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor and at least 50% of the enriched population has a CD45RAint CD45ROint CD95+CD127+CD27+ phenotype.
Treatment of an HIV-infected subject
Administering the enriched T cell population characterized by the CD45RAint CD45ROint CD95+CD127+TCF7+CD27+ phenotype and modified to be devoid of a functional CCR5 and/or CXCR4 HIV co-receptor to an HIV-infected subject, including in the context of ongoing and/or previous antiretroviral therapy, in an amount effective to promote specified outcomes.
Overall, the claims are directed to a marker-defined enriched CD4+ T cell population with increased TCF7 and genetic modification to be devoid of functional CCR5 and/or CXCR4 HIV co-receptor, together with administration of that population to an HIV-infected subject, optionally under antiretroviral therapy, to promote the stated outcomes.
Stated Advantages
Sustained increases in absolute CD4 cell numbers.
Restoration of HIV-specific T cell immunity.
Substantial HIV reservoir decay.
Documented Applications
Administration of the enriched T cell population to an HIV-infected subject to promote sustained increases in absolute CD4 cell numbers, restoration of HIV-specific T cell immunity, or substantial decay in the HIV reservoir.
Treating an HIV-infected subject by administering the isolated enriched gene-modified CD4+ T cell population, including in the setting of ongoing and/or previous antiretroviral therapy.
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