Method of treating autoimmune and inflammatory diseases using B cells
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Publication Number
US-12544439-B2
Publication Date
2026-02-10
Expiration Date
Abstract
GITRL+ IgDlow/− B cells as well as methods of making and using said cells are described herein. Also described are methods for treating an autoimmune disease or an inflammatory condition in a subject in need thereof of using said B cells. The B cells may be GITRL+ IgDlowCCR7+ CXCR5+ B cells or GITRL+ IgDlow CCR7+ CXCR5+ CD23+ CD24+ B cells.
Core Innovation
The invention provides a method for treating an autoimmune disease or an inflammatory condition in a subject in need thereof by administering therapeutically effective amounts of glucocorticoid-induced tumor necrosis factor receptor ligand positive (GITRL+), immunoglobulin D low (IgDlow), CCR7+ CXCR5+ B cells. The described B-cell population is defined by the expression of GITRL together with an IgD low state and the CCR7 and CXCR5 chemokine receptor markers.
The approach is further characterized by using GITRL+ IgDlow B cells that stimulate CD4+ Foxp3+ T regulatory cell proliferation, with the described effect characterized as GITRL-dependent and not dependent on IL-10. The described BDL also retain a stable mature subset phenotype, and exhibit distinct chemokine and migration traits consistent with CCR7 and CXCR5.
The disclosure also includes embodiments in which the B cells are administered by adoptive cell transfer or infusion, and embodiments using engineered B-cell variants having altered functional characteristics, including increased GITRL and decreased or silenced IgD. Additional optional engineered features include suicide genes selected from HSV-TK, iCasp9, mTMPK, or human CD20, and optional expression knockouts such as CIITA or -microglobulin.
Claims Coverage
Independent claim clm-00001 covers a method of treating autoimmune disease or inflammatory condition by administering therapeutically effective amounts of a defined B-cell phenotype characterized by GITRL positivity together with IgDlow, CCR7+, and CXCR5+ markers. Dependent claim refinements add additional B-cell marker constraints and specify downstream immunological effects and/or delivery/engineering features.
Treating autoimmune or inflammatory disease with GITRL+ IgDlow CCR7+ CXCR5+ B cells
Administering to a subject in need thereof a therapeutically effective amount of GITRL+ IgDlow, CCR7+, CXCR5+ B cells to treat an autoimmune disease or an inflammatory condition.
Stimulating CD4+ Foxp3+ T regulatory cell proliferation using GITRL+ IgDlow B cells
Using the method to administer GITRL+ IgD low B cells that stimulate proliferation of CD4+ Foxp3+ T regulatory cells.
Adoptive cell transfer administration of the B cells
Administering the GITRL+ IgDlow, CCR7+, CXCR5+ B cells via adoptive cell transfer.
Selecting a B-cell phenotype lacking CIITA
Performing the method using a B cell that does not express the class II major histocompatibility complex transactivator (CIITA).
Engineered B cells with selectable suicide gene(s)
Performing the method using an engineered B cell that includes a suicide gene selected from HSV-TK, iCasp9, mTMPK, or human CD20.
Across the independent claim and its refinements, the core inventive coverage centers on administering GITRL+ IgDlow CCR7+ CXCR5+ B cells for treating autoimmune or inflammatory conditions, with described downstream stimulation of CD4+ Foxp3+ T regulatory cell proliferation and optional constraints or enhancements including adoptive transfer delivery and engineered suicide gene features.
Stated Advantages
GITRL-dependent stimulation of CD4+ Foxp3+ T regulatory cell proliferation that is IL-10-independent.
Retention of a stable mature subset phenotype by the described B-cell population.
Distinct chemokine/migration traits associated with CCR7 and CXCR5.
Documented Applications
Treatment of autoimmune disease or inflammatory condition (as a general use case).
Supporting preclinical evidence is described in association with experimental autoimmune encephalomyelitis (EAE).
Supporting preclinical evidence is described in association with contact hypersensitivity (CHS).
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