Intracellular delivery of biomolecules to modify immune response
AssigneeStemcell Technologies Canada Inc.
InventorsScott Loughhead, LeeAnn Talarico, Alfonso Vicente-Suarez, Matt Booty, Howard Bernstein, Katarina Blagovic, Armon R. Sharei, Kelan Hlavaty
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Abstract
The present application provides T cells comprising an antigen and an adjuvant, methods of manufacturing such T cells, and methods of using such T cells, such as for modulating an immune response in an individual.
Claims7
A modified T cell comprising an antigen and an adjuvant, wherein the antigen is exogenous to the modified T cell and comprises an immunogenic epitope, wherein the antigen and the adjuvant are present in the cytosol and/or endosomes of the modified T cell, and wherein the antigen is capable of being processed into an MHC class I-restricted peptide and/or an MHC class II-restricted peptide, and wherein the immunogenic epitope is derived from a disease-associated antigen, a non-self antigen, a tumor antigen, a viral antigen, or an allergen-derived antigen,
- wherein the disease-associated antigen, the non-self antigen, the tumor antigen, or the viral antigen comprises an amino acid sequence of any one of SEQ ID Nos:
- 18, 21, 23 and 25, or wherein the allergen-derived antigen is presented by the modified T cell within 2-4 hours.
A modified T cell comprising an antigen and an adjuvant, wherein the antigen comprises an immunogenic epitope, prepared by a process comprising the steps of:
- a) passing a cell suspension comprising an input T cell through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input T cell in the suspension, thereby causing perturbations of the input T cell large enough for the antigen and the adjuvant to pass through to form a perturbed input T cell;
- and
- b) incubating the perturbed input T cell with the antigen for a sufficient time ranging from 1 second to at least 30 minutes to allow the antigen to enter the perturbed input T cell, thereby generating the modified T cell comprising the antigen and the adjuvant, wherein the antigen is capable of being processed into an MHC class I-restricted peptide and/or an MHC class Il-restricted peptide, and
- wherein the immunogenic epitope is derived from a disease-associated antigen, a non-self antigen, a tumor antigen, a viral antigen, or an allergen-derived antigen,
- wherein the disease-associated antigen, the non-self antigen, the tumor antigen, or the viral antigen comprises an amino acid sequence of any one of SEQ ID Nos:
- 18, 21, 23 and 25, or
- wherein the allergen-derived antigen is presented by the modified T cell within 2-4 hours.
A modified T cell comprising an antigen and an adjuvant, wherein the antigen comprises an immunogenic epitope, prepared by a process comprising the steps of:
- a) passing a cell suspension comprising an input T cell comprising the adjuvant through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input T cell in the suspension, thereby causing perturbations of the input T cell large enough for the antigen to pass through to form a perturbed input T cell;
- and
- b) incubating the perturbed input T cell with the antigen for a sufficient time ranging from 1 second to at least 30 minutes to allow the antigen to enter the perturbed input T cell, thereby generating the modified T cell comprising the antigen and the adjuvant, wherein the antigen is capable of being processed into an MHC class I-restricted peptide and/or an MHC class II-restricted peptide, and
- wherein the immunogenic epitope is derived from a disease-associated antigen, a non-self antigen, a tumor antigen, a viral antigen, or an allergen-derived antigen,
- wherein the disease-associated antigen, the non-self antigen, the tumor antigen, or the viral antigen comprises an amino acid sequence of any one of SEQ ID Nos:
- 18, 21, 23 and 25, or wherein the allergen-derived antigen is presented by the modified T cell within 2-4 hours.
A modified T cell comprising an antigen and an adjuvant, wherein the antigen comprises an immunogenic epitope, prepared by a process comprising the steps of:
- a) passing a cell suspension comprising an input T cell comprising the antigen through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input T cell in the suspension, thereby causing perturbations of the input T cell large enough for the adjuvant to pass through to form a perturbed input T cell;
- and
- incubating the perturbed input T cell with the antigen for a sufficient time ranging from 1 second to at least 30 minutes to allow the antigen to enter the perturbed input T cell, thereby generating the modified T cell comprising the antigen and the adjuvant, wherein the antigen is capable of being processed into an MHC class I-restricted peptide and/or an MHC class II-restricted peptide, and
- wherein the immunogenic epitope is derived from a disease-associated antigen, a non-self antigen, a tumor antigen, a viral antigen, or an allergen-derived antigen,
- wherein the disease-associated antigen, the non-self antigen, the tumor antigen, or the viral antigen comprises an amino acid sequence of any one of SEQ ID Nos:
- 18, 21, 23 and 25, or
- wherein the allergen-derived antigen is presented by the modified T cell within 2-4 hours.
A pharmaceutical composition comprising a modified T cell comprising an antigen and an adjuvant, wherein the antigen comprises an immunogenic epitope, prepared by a process comprising the steps of:
- a) passing a cell suspension comprising an input T cell through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input T cell in the suspension, thereby causing perturbations of the input T cell large enough for the antigen to pass through to form a perturbed input T cell;
- and
- b) incubating the perturbed input T cell with the antigen and the adjuvant for a sufficient time ranging from 1 second to at least 30 minutes to allow the antigen to enter the perturbed input T cell;
- thereby generating the pharmaceutical composition comprising the modified T cell comprising the antigen and the adjuvant, wherein the antigen is capable of being processed into an MHC class I-restricted peptide and/or an MHC class II-restricted peptide, and
- wherein the immunogenic epitope is derived from a disease-associated antigen, a non-self antigen, a tumor antigen, a viral antigen, or an allergen-derived antigen,
- wherein the disease-associated antigen, the non-self antigen, the tumor antigen, or the viral antigen comprises an amino acid sequence of any one of SEQ ID Nos:
- 18, 21, 23 and 25, or
- wherein the allergen-derived antigen is presented by the modified T cell within 2-4 hours.
Dependencies are inferred from the claim text.