Generation of broadly-specific, virus-immune cells targeting multiple HIV antigens for preventive and therapeutic use

A composition comprising HIV-antigen specific CD4+ and CD8+ T-cells produced by a method 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 CD4+ and CD8+ HIV-antigen-specific T-cells that recognize the at least one HIV-peptide antigen;
• (e) contacting HIV-antigen-specific CD4+ and CD8+ 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 CD4+ and CD8+ T-cells;
• and
• (g) recovering HIV-antigen-specific T-cells that recognize the at least one HIV-peptide antigen;
• wherein MOGS expression has been knocked down by contacting, maintaining or culturing the T-cells, precursor T-cells or HIV-antigen specific T-cells in a medium in vitro or ex vivo containing at least one drug that inhibits or inactivates MOGS;
• or wherein MOGS expression has been knocked down by genetically modifying the T-cell, T-cell precursor, or HIV-antigen specific T cell to attenuate or knock out MOGS expression;
• or by modifying the T-cell, T-cell precursor, or HIV-antigen specific T-cell using RNAi or by expression of intrabodies to attenuate or knock out MOGS expression.