Granted Patent B2

US 12,599,656 · App. 16/980,341 · Granted Apr 14, 2026

Inventors: Scott Loughhead (Durham, NC); LeeAnn Talarico (Milton, MA); Alfonso Vicente-Suarez (Brookline, MA); Matt Booty (Watertown, MA); Howard Bernstein (Cambridge, MA); Katarina Blagovic (Cambridge, MA); Armon R. Sharei (Somerville, MA); Kelan Hlavaty (Belmont, MA); Melissa Myint (Watertown, MA)

A61K39/12A61K33/243A61K40/11A61K40/13A61K40/19A61K40/24A61K40/428A61K40/46A61K45/06A61P35/00A61K2039/55516A61K2039/55561A61K2039/585A61K2239/31A61K2239/39C12N2710/20034

Abstract

Claims (20)

1 . A composition comprising modified immune cells, wherein the immune cells are modified to comprise intracellularly a CpG ODN and an HPV antigen with at least 90% similarity to any one of SEQ ID NOs:18-25.

2 . The composition in claim 1 , wherein the modified immune cells are prepared by

a) passing a cell suspension comprising an input cell through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input cell in the suspension, thereby causing perturbations of the input cell large enough for the HPV antigen and the CpG ODN to pass through to form a perturbed input cell; and

b) incubating the perturbed input cell with the HPV antigen and the CpG ODN for a sufficient time to allow the HPV antigen and the CpG ODN to enter the perturbed input cell; thereby generating the modified immune cells.

3 . A composition comprising modified immune cells, wherein the immune cells are modified to comprise an HPV antigen, wherein the HPV antigen comprises an amino acid sequence with at least 90% similarity to any one of SEQ ID NOs:18-25.

4 . The composition in claim 3 , wherein the modified immune cells are prepared by

a) passing a cell suspension comprising an input cell through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input cell in the suspension, thereby causing perturbations of the input cell large enough for the IPV antigen to pass through to form a perturbed input cell; and

b) incubating the perturbed input cell with the HPV antigen for a sufficient time to allow the HPV antigen to enter the perturbed input cell;

thereby generating the modified immune cells.

5 . A composition comprising an antigen, wherein the antigen comprises an amino acid sequence with at least 90% similarity to SEQ ID NO:23.

6 . A plurality of modified peripheral blood mononuclear cells (PBMCs), wherein the PBMCs are modified to comprise an antigen and an increased expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α compared to a plurality of unmodified PBMCs, wherein the expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10 or TNF-α is increased upon incubation of the plurality of modified PBMCs with an adjuvant, and wherein the antigen is exogenous to the modified PBMCs.

7 . A plurality of modified PBMCs, wherein the PBMCs are modified to comprise an antigen and an adjuvant and an increased expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α compared to a plurality of unmodified PBMCs, wherein the expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α is increased upon incubation of the plurality of modified PBMCs with a second adjuvant, and wherein the antigen is exogenous to the modified PBMCs.

8 . A plurality of modified PBMCs, wherein the PBMCs are modified to comprise an antigen and an increased expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α compared to a plurality of unmodified PBMCs, prepared by a process comprising the steps of:

a) passing a cell suspension comprising a plurality of input PBMCs through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input PBMCs in the suspension, thereby causing perturbations of the input PBMCs large enough for the antigen to pass through to form a plurality of perturbed input PBMCs;

b) incubating the plurality of perturbed input PBMCs with the antigen for a sufficient time to allow the antigen to enter the perturbed input PBMCs, thereby generating a plurality of modified PBMCs comprising the antigen; and

c) incubating the plurality of modified PBMCs comprising the antigen with an adjuvant for a sufficient time to generate the modified PBMCs comprising the antigen with increased expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α.

9 . A plurality of modified PBMCs, wherein the PBMCs are modified to comprise an antigen and an increased expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α compared to a plurality of unmodified PBMCs, prepared by a process comprising the steps of;

a) incubating a plurality of input PBMCs with an adjuvant for a sufficient time to generate PBMCs with increased expression of one or more of IFN-γ, IL-6, MCP-1, MIP-1β, IP-10, or TNF-α;

b) passing a cell suspension comprising the plurality of input PBMCs through a cell-deforming constriction, wherein a diameter of the constriction is a function of a diameter of the input PBMCs in the suspension, thereby causing perturbations of the input PBMCs large enough for the antigen to pass through to form a plurality of perturbed input PBMCs; and

c) incubating the plurality of perturbed input PBMCs with the antigen for a sufficient time to allow the antigen to enter the perturbed input PBMCs, thereby generating the plurality of modified PBMCs comprising the antigen.

Assignments (3)

Continuity (4)

References Cited (173)