Methods and compositions for the activation of gamma-delta T-cells
Inventors
Pauza, Charles David • Li, Haishan • Lahusen, Tyler • Liou, Mei-Ling
Assignees
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Publication Number
US-11534450-B2
Publication Date
2022-12-27
Expiration Date
Abstract
The present invention relates generally to methods and compositions for gene therapy and immunotherapy that activate gamma delta T-cells, and in particular, can be used in the treatment of various cancers and infectious diseases.
Core Innovation
The invention relates to activating GD T cells, or in a broader form a lymphocyte cell, by contacting a target cell with a bisphosphonate drug and infecting the target cell, in the presence of the lymphocyte, with a viral delivery system that encodes at least one genetic element comprising a small RNA capable of inhibiting production of FDPS. The activation results from the combined presence of the bisphosphonate drug and the viral-delivery-encoded small RNA that inhibits FDPS production.
The encoded small RNA is a genetic element within the viral delivery system and is capable of inhibiting production of an enzyme of the mevalonate pathway. In the GD T cell embodiment, the inhibited enzyme is FDPS, and the method activates the lymphocyte cell.
The activation is described by increased TNF-α expression by the GD T cell, and the small RNA is specified as microRNA or shRNA. In certain forms, the activated lymphocyte kills the target cell.
Claims Coverage
The partial content provides two independent claims. Each claim centers on a three-part combination: bisphosphonate drug contact, infection of a target cell in the presence of the lymphocyte, and encoded small RNA that inhibits production of a mevalonate-pathway enzyme, resulting in lymphocyte activation.
Activating a GD T cell by bisphosphonate contact and viral small RNA infection
Contacting a target cell with a bisphosphonate drug, and infecting, in the presence of the GD T cell, the target cell with a viral delivery system that encodes at least one genetic element comprising a small RNA capable of inhibiting production of FDPS, wherein the GD T cell is activated.
Activating a lymphocyte cell by bisphosphonate contact and viral small RNA infection
Contacting a target cell with a bisphosphonate drug, and infecting, in the presence of the lymphocyte cell, the target cell with a viral delivery system that encodes at least one genetic element comprising a small RNA capable of inhibiting production of an enzyme of the mevalonate pathway, wherein the lymphocyte cell is activated.
Across the two independent claims, the core inventive concept is activation of lymphocytes, including GD T cells, by combining bisphosphonate drug contact with infection of a target cell using a viral delivery system encoding small RNA that inhibits FDPS or another mevalonate-pathway enzyme.
Stated Advantages
Increased TNF-α expression by the GD T cell.
In certain forms, killing of the target cell by an activated lymphocyte.
Documented Applications
No documented applications found
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