Recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells

摘要

Disclosed herein are recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells. The recombinant human progenitor cells are made by transducing a human hematopoietic stem cell with a vector having a nucleic acid molecule which encodes a human T cell receptor specific to a virus, such as Human Immunodeficiency Virus, or an epitope thereof. The recombinant human progenitor cells differentiate and mature into the engineered human thymocytes and the engineered human T cells. Also disclosed herein are methods of inhibiting, reducing or treating a viral infection in a subject, such as a human subject, which comprises administering recombinant human progenitor cells, engineered human thymocytes, and/or engineered human T cells to the subject.

主权项

1. A method of producing an engineered thymocyte or an engineered T cell which comprises
spectratyping-based cloning to obtain a nucleic acid molecule which encodes a human T cell receptor specific for a virus or an epitope thereof; transducing a human hematopoietic stem cell with a vector containing the nucleic acid molecule to give a recombinant progenitor cell; and differentiating or developing the recombinant progenitor cell into the engineered thymocyte by subjecting the recombinant progenitor cell to a thymus tissue, and then optionally maturing the engineered thymocyte into the engineered T cell, and wherein the spectratyping-based cloning comprises obtaining peripheral blood mononuclear cells from a subject infected with the virus and dividing the peripheral blood mononuclear cells into a first portion and a second portion; culturing the first portion with the virus or the epitope thereof; spectratyping the TCR α-genes and TCR β-genes in the first portion to obtain a first fingerprint; spectratyping the TCR α-genes and TCR β-genes in the second portion to obtain a second fingerprint; selecting a TCR α-gene and a TCR β-gene in the first portion which are not present in the second portion; and recombinantly joining the selected TCR α-gene and TCR β-gene to give the nucleic acid molecule.