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 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.
Claims149
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, and wherein the adjuvant is present intracellularly.
A modified T cell comprising an antigen comprising the amino acid sequence of any one of SEQ ID NOs:
- 18-25.
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 and the adjuvant for a sufficient time to allow the antigen and the adjuvant to enter the perturbed input T cell;
- thereby generating the modified T cell comprising the antigen and adjuvant.
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 to allow the antigen to enter the perturbed input T cell, thereby generating the modified T cell comprising the antigen and the adjuvant.
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
- b) incubating the perturbed input T cell with the adjuvant for a sufficient time to allow the adjuvant to enter the perturbed input T cell, thereby generating the modified T cell comprising the antigen and the adjuvant.
A method for modulating an immune response in an individual, comprising:
- a) administering a modified T cell comprising an antigen comprising the amino acid sequence of any one of SEQ ID NOs:
- 18-25 to the individual;
- and
- b) administering an adjuvant to the individual.
A method for modulating an immune response in an individual, comprising:
- 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 an antigen and an adjuvant to pass through to form a perturbed input T cell, wherein the antigen comprises an immunogenic epitope;
- b) incubating the perturbed input T cell with the antigen and the adjuvant for a sufficient time to allow the antigen and the adjuvant to enter the perturbed input T cell, thereby generating a modified T cell comprising the antigen and adjuvant;
- and
- c) administering the modified T cell to the individual.
A method for modulating an immune response in an individual, comprising:
- a) passing a cell suspension comprising an input T cell comprising an 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 an antigen to pass through to form a perturbed input T cell, wherein the antigen comprises an immunogenic epitope;
- b) incubating the perturbed input T cell with the antigen for a sufficient time to allow the antigen to enter the perturbed input T cell, thereby generating a modified T cell comprising the antigen and the adjuvant;
- and
- c) administering the modified T cell to the individual.
A method for modulating an immune response in an individual, comprising:
- a) passing a cell suspension comprising an input T cell comprising an antigen through a cell-deforming constriction, wherein the antigen comprises an immunogenic epitope, 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 an adjuvant to pass through to form a perturbed input T cell;
- b) incubating the perturbed input T cell with the adjuvant for a sufficient time to allow the adjuvant to enter the perturbed input T cell, thereby generating a modified T cell comprising the antigen and the adjuvant;
- and
- c) administering the modified T cell to the individual.
A method for modulating an immune response in an individual, comprising:
- 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 an antigen to pass through to form a perturbed input T cell, wherein the antigen comprises an immunogenic epitope;
- b) incubating the perturbed input T cell with the antigen for a sufficient time to allow the antigen to enter the perturbed input T cell, thereby generating a modified T cell comprising the antigen;
- c) administering the modified T cell to the individual;
- and
- d) administering an adjuvant to the individual.
A method for modulating an immune response in an individual, comprising:
- administering to the individual a modified T cell associated with an antigen, wherein the modified T cell is prepared by a process comprising the steps of:
- a) incubating an input T cell with an antigen and/or an adjuvant for a sufficient time to allow the antigen to associate with the cell surface of the input T cell, wherein the antigen comprises an immunogenic epitope, thereby generating a modified T cell associated with the antigen;
- and
- b) administering the modified T cell to the individual.
A composition comprising the modified T cell for use in a method of treatment of the human or animal body by surgery, therapy or diagnosis, wherein the modified T cell comprising an antigen comprising the amino acid sequence of any one of SEQ ID NOs:
- 18-25.
A composition comprising the modified T cell for use in a method of modulating an immune response in an individual, wherein the modified T cell comprising an antigen comprising the amino acid sequence of any one of SEQ ID NOs:
- 18-25.
A composition comprising the modified T cell for use in a method of treatment of the human or animal body by surgery, therapy or diagnosis, wherein the modified T cell is prepared by the method comprising:
- 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 an antigen and an adjuvant to pass through to form a perturbed input T cell, wherein the antigen comprises an immunogenic epitope;
- b) incubating the perturbed input T cell with the antigen and the adjuvant for a sufficient time to allow the antigen and the adjuvant to enter the perturbed input T cell, thereby generating a modified T cell comprising the antigen and adjuvant.
A composition comprising the modified T cell for use in a method of modulating an immune response in an individual, wherein the modified T cell is prepared by the method comprising:
- 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 an antigen and an adjuvant to pass through to form a perturbed input T cell, wherein the antigen comprises an immunogenic epitope;
- b) incubating the perturbed input T cell with the antigen and the adjuvant for a sufficient time to allow the antigen and the adjuvant to enter the perturbed input T cell, thereby generating a modified T cell comprising the antigen and adjuvant.
Dependencies are inferred from the claim text.