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US 11,999,967 B2Granted
Generating HPV antigen-specific cells from a naive T cell population
AssigneeChildren's National Medical Center
InventorsCatherine M. Bollard, Conrad Russell Cruz, Patrick J. Hanley, Michael Keller
Life of this patent
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Abstract
Safe, rapid and efficient methods for producing antigen-specific T cells recognizing human papilloma virus or HPV antigens.
Claims26
A process for producing an HPV antigen-specific T cell comprising:
- (a) dividing a sample of mononuclear cells from a subject naïve to HPV antigens into several portions;
- (b) stimulating a first portion of said sample with PHA or another mitogen and with IL-2 to produce ATCs activated T cells (“ATCs”) that serve antigen presenting functions during subsequent stimulations and optionally treating the ATCs with radiation or another agent to inhibit their outgrowth;
- (c) separating T cells and T-cell precursor cells from dendritic cells and dendritic precursor cells in a second portion of the sample to form a T cell portion and a dendritic cell portion;
- (d) cryopreserving or otherwise reserving the T cells and T-cell precursor cells in the T cell portion;
- (e) differentiating the dendritic cells and dendritic precursor cells in the dendritic cell portion of the sample with cytokine(s) or other agent(s) that generate and mature dendritic cells and with at least one HPV peptide antigen or HPV antigen mix to produce antigen-presenting dendritic cells that present at least one HPV peptide antigen, and optionally treating said antigen-presenting dendritic cells with radiation or another agent sufficient to inhibit their outgrowth;
- (f) stimulating the cryopreserved or otherwise reserved T cells and T-cell precursor cells from the T cell portion in (d) with the dendritic antigen-presenting cells produced from the dendritic cell portion in (e) in the presence of IL-7 and IL-15 to produce antigen-specific T cells that recognize the at least one HPV peptide antigen;
- (g) stimulating antigen-specific T cells produced by (f) with the ATCs of (b) in the presence of the at least one HPV peptide antigen, optionally, in the presence of K562 cells or other accessory cells in the presence of IL-2 and/or IL-15;
- optionally, repeating (g) one or more times;
- and
- (h) recovering HPV antigen-specific T cells that recognize at least one peptide antigen.
7 more elements
Dependencies are inferred from the claim text.