GENERATION OF BROADLY-SPECIFIC, VIRUS-IMMUNE CELLS TARGETING MULTIPLE HIV ANTIGENS FOR PREVENTIVE AND THERAPEUTIC USE

摘要

Compositions for T cell-based immunotherapy of HIV, HIV-associated malignancies, HIV-associated viral infections, or other HIV-related complications. Modified T cells that are resistant to invasion or infection with HIV, such as T-cells modified to decrease or eliminate expression of mannosyl-oligosacharide glucosidase enzyme (“MOGS”). Methods for producing such compositions by expanding HIV-specific T cells from different sources to recognize multiple HIV antigens.

主权项

1. A method for producing HIV-antigen-specific T cells resistant to infection by HIV comprising:
(a) separating T-cells or T-cell precursors from dendritic cells or dendritic cell precursors in a hematopoietic cell sample, (b) producing blasts by contacting a portion of a hematopoietic cell sample, or a portion of said separated T-cells or T-cell precursors, with PHA or another mitogen, or by CD3/CD28 stimulation, and, optionally, treating the blasts with radiation or another agent to inhibit their outgrowth; (c) contacting the dendritic cells or dendritic precursor cells separated in (a) with cytokine(s) or other agent(s) that generate and mature dendritic cells and with at least one HIV peptide antigen to produce HIV-antigen-presenting dendritic cells that present at least one HIV-peptide antigen, and, optionally, treating said HIV-antigen-presenting dendritic cells with radiation or another agent sufficient to inhibit their outgrowth; (d) contacting the T-cells or T-cell precursors from (a) with the dendritic antigen-presenting cells produced in (c) in the presence of IL-7, IL-12 and/or IL-15 to produce HIV-antigen-specific T-cells that recognize the at least one HIV-peptide antigen; (e) contacting HIV-antigen-specific T-cells produced by (d) with the blasts of (b) in the presence of the at least one HIV-peptide antigen, optionally, in the presence of K562 cells or other accessory cells in the presence of IL-2 and/or IL-15; (f) optionally, repeating (e) one or more times to restimulate and/or expand the HIV-antigen specific T-cells; and (g) recovering HIV-antigen-specific T-cells that recognize the at least one HIV-peptide antigen.