Methods for generating functional therapeutic B cells ex-vivo
AssigneeGeorgia Tech Research Corporation
InventorsKrishnendu Roy, Kyung-Ho Roh
Life of this patent
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Abstract
The various embodiments of the disclosure relate generally to processes, methods, and systems for generating functional B cells ex vivo. It is particularly useful for ex vivo generation of antigen-specific germinal-center (GC) like B cells that are capable of efficient B cell expansion, immunoglobulin (Ig) class switching/class switching recombination (CSR), expression of germinal B cell phenotypes, antibody secretion, and somatic hypermutation (SHM) and resulting affinity maturation center phenotypes.
Claims18
A method of ex vivo generation of B cells in a synthetic germinal center comprising:
- exposing naïve B cells to a protein comprising the amino acid sequence of SEQ ID NO:
- 18 and to an antigen in the synthetic germinal center, wherein at least one of the protein or the antigen is presented on a three dimensional surface;
- and
- obtaining B cells with one or more characteristics selected from the group consisting of efficient B cell proliferation, class switching recombination (CSR), expression of activated B cell phenotypes, expression of germinal center B cell phenotypes, expression of plasma cell phenotypes, expression of memory B cell phenotypes, expression of regulatory B cell phenotypes, antibody secretion, and somatic hypermutation (SHM) and resulting affinity maturation.
A method of ex vivo generation of B cells in a synthetic germinal center comprising:
- exposing naïve B cells to a protein comprising the amino acid sequence of SEQ ID NO:
- 18 and to an antigen selected from the group consisting of polypeptides and proteins, at least one kind of the protein comprising the amino acid sequence of SEQ ID NO:
- 18 or the antigen is in a soluble form;
- eliminating at least a portion of dead B cells;
- and
- obtaining antigen-specific B cells with one or more characteristics selected from the group consisting of efficient B cell proliferation, class switching recombination (CSR), expression of activated B cell phenotypes, expression of memory B cell phenotypes, expression of regulatory B cell phenotypes, expression of plasma cell phenotypes, antibody secretion, and somatic hypermutation (SHM) and resulting affinity maturation.
A method of ex vivo generation of B cells comprising:
- exposing naïve B cells to a protein comprising the amino acid sequence of SEQ ID NO:
- 18 and to an antigen, wherein at least one of the protein or the antigen is presented on a three dimensional surface of a microbead or a microcarrier;
- and
- obtaining B cells with one or more characteristics selected from the group consisting of efficient B cell expansion, efficient B cell proliferation, class switching recombination (CSR), expression of activated B cell phenotypes, expression of germinal center B cell phenotypes, expression of plasma cell phenotypes, expression of memory B cell phenotypes, expression of regulatory B cell phenotypes, antibody secretion, and somatic hypermutation (SHM) and resulting affinity maturation.
Dependencies are inferred from the claim text.