Methods to determine treatment efficacy with gamma-delta t cells
AssigneeThe Trustees of the University of Pennsylvania
InventorsXiaowei XU, Huaishan WANG, Hui CHEN, Lingling OU
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Abstract
The present disclosure provides methods for selecting donors for γδT cell-based immunotherapy. The disclosure also provides methods for expanding and activating γδ T cells with improved cytotoxicity toward tumor cells and reduced T cell exhaustion. Pharmaceutical compositions comprising the expanded γδ T cells and methods of treatment are also provided.
Claims87
A method of selecting a donor for γδ T cell-based immunotherapy, the method comprising assessing the expansion capacity of a population of γδ T cells from a subject, wherein when the expansion capacity is high, the subject is selected as a donor, and wherein when the expansion capacity is low, the subject is not selected as a donor.
A method of selecting a donor for γδ T cell-based immunotherapy, the method comprising measuring the basal level of Vδ2 T cells in a subject, wherein when the basal level of Vδ2 T cells is high, the subject is selected as a donor, and wherein when the basal level of Vδ2 T cells is low, the subject is not selected as a donor.
A method of treating a disease or disorder in a subject in need thereof with a γδ T cell-based immunotherapy, the method comprising:
- selecting a donor for the γδ T cell-based immunotherapy by assessing the expansion capacity of a population of γδ T cells from a healthy subject,
- wherein when the expansion capacity is high, the healthy subject is selected as a donor, and a γδ T cell-based immunotherapy comprising the γδ T cells from the donor is administered to the subject in need thereof, thus treating the disease or disorder, and
- wherein when the expansion capacity is low, the healthy subject is not selected as a donor and an alternative treatment is administered or a different donor is selected.
A method of treating a disease or disorder in a subject in need thereof with a γδ T cell-based immunotherapy, the method comprising:
- assessing the expansion capacity of a population of γδ T cells from the subject, wherein when the expansion capacity is high, the subject is administered a γδ T cell-based immunotherapy comprising the γδ T cells from the subject, thus treating the disease or disorder, and
- wherein when the expansion capacity is low, the γδ T cell-based immunotherapy is not administered and an alternative treatment is administered and/or a new donor is selected.
A method of treating a disease or disorder in a subject in need thereof with a γδ T cell-based immunotherapy, the method comprising:
- selecting a donor for the γδ T cell-based immunotherapy by measuring the basal level of Vδ2 T cells in a healthy subject,
- wherein when the basal level of Vδ2 T cells is high, the healthy subject is selected as a donor, and a γδ T cell-based immunotherapy comprising the γδ T cells from the donor is administered to the subject in need thereof, thus treating the disease or disorder, and
- wherein when the basal level of Vδ2 T cells is low, the healthy subject is not selected as a donor, and an alternative treatment is administered or a different donor is selected.
A method for expanding and activating a plurality of γδ T cells, the method comprising contacting a population of cells comprising a plurality of γδ T cells with:
- (a) at least one γδ T cell receptor (γδTCR) activator, wherein the γδTCR activator is not zoledronate and is a weaker γδTCR activator than zoledronate;
- and
- (b) a toll-like receptor (TLR) agonist.
A method for expanding and activating a plurality of γδ T cells, the method comprising contacting a population of cells comprising a plurality of γδ T cells with an antibody-conjugated bead,
- wherein the antibody-conjugated bead comprises a bead attached to a plurality of at least one anti-γδ T cell receptor (anti-γδTCR) antibody and/or anti-γδTCR antigen-binding domain;
- and
- wherein the method does not comprise contacting the population of cells with zoledronate.
Dependencies are inferred from the claim text.