Methods and agents for modulating adoptive immunotherapy

A method of modulating an immune response at a focus of interest in a subject in need thereof, the method comprising:

• administering a xenobiotic fuel-enabled bioengineered immune cell to said subject said bioengineered immune cell comprising:
• (a) at least one vector comprising at least one nucleic acid encoding at least one transporter protein or a functional fragment thereof for transport of the xenobiotic fuel into the bioengineered immune cell;
• (b) at least one vector comprising at least one nucleic acid encoding at least one protein or a functional fragment thereof for enabling the metabolizing of the xenobiotic fuel in the bioengineered immune cell;
• or
• (c) a combination of (a) and (b);
• administering the xenobiotic fuel to said subject;
• wherein said modulating the immune response comprises stimulating said immune response or suppressing said immune response.

A method of modulating an immune response at the site of a solid tumor or infection, said method comprising:

• administering a cellobiose-enabled bioengineered T cell to said subject adjacent to a solid tumor or infection, said cellobiose-enabled bioengineered T cell comprising a vector comprising a nucleic acid encoding a cellodextrin transporter protein or a functional fragment thereof and a vector comprising a nucleic acid encoding a beta-glucosidase protein or a functional fragment thereof;
• and administering cellobiose to said subject or implanting a scaffold that releases cellobiose adjacent to said solid tumor or infection, said modulating the immune response comprising increasing proliferation of cytotoxic T cells;
• increasing proliferation of helper T cells;
• maintaining the population of helper T cells at the site of said tumor;
• activating cytotoxic T cells at the site of said solid tumor or infection;
• or any combination thereof.

A method of modulating an immune response at the site of a solid tumor or infection, said method comprising:

• administering a cellobiose-enabled bioengineered B cell to said subject adjacent to a solid tumor or infection, said cellobiose-enabled bioengineered B cell comprising a vector comprising a nucleic acid encoding a cellodextrin transporter protein or a functional fragment thereof and a vector comprising a nucleic acid encoding a beta-glucosidase protein or a functional fragment thereof;
• and administering cellobiose to said subject or implanting a scaffold that releases cellobiose adjacent to said solid tumor or infection, said modulating the immune response comprising increasing production of antibodies from the B cell;
• increasing isotype switching;
• increasing affinity maturation;
• or any combination thereof.

A method of modulating an immune response at a focus of interest of an autoimmune disease, an allergic reaction, a localized infection or an infectious disease, an injury or other damage, a transplant or other surgical site, or a symptom thereof, or a combination thereof, in a subject in need thereof, comprising administering to said subject a bioengineered T regulatory (Treg) cell, adjacent to said focus of interest, said cellobiose-enabled bioengineered Treg cell comprising a vector comprising a nucleic acid encoding a cellodextrin transporter protein or a functional fragment thereof and a vector comprising a nucleic acid encoding a beta-glucosidase protein or a functional fragment thereof;

• and administering cellobiose to said subject or implanting a scaffold that release said cellobiose adjacent to said focus of interest;
• wherein said regulating the immune response comprises decreasing proliferation of cytotoxic T cells;
• decreasing proliferation of helper T cells;
• suppressing cytotoxic T cells at the site of said focus of interest;
• or any combination thereof.

A vector comprising at least one nucleic acid sequence encoding at least one protein for modifying a bioengineered cell to enable metabolism of a xenobiotic fuel in the cell, the xenobiotic fuel not metabolized by a corresponding unmodified cell, the vector comprising:

• (a) a promoter, the promoter operably linked to (i) a nucleic acid encoding a transporter protein or a functional fragment thereof for transport of the xenobiotic fuel into the bioengineered cell;
• (ii) a nucleic acid encoding a protein or a functional fragment thereof for enabling the metabolizing of the xenobiotic fuel in the bioengineered cell;
• or (iii) a combination of (i) and (ii);
• and
• (b) a selective marker.

A method of making a xenobiotic-enabled bioengineered cell, modified to metabolize a xenobiotic fuel, the xenobiotic fuel not metabolized by a corresponding unmodified cell, the method comprising:

• (a) selecting a xenobiotic fuel;
• (b) selecting a transporter protein or functional fragment thereof for transport of the xenobiotic fuel and obtaining a nucleic acid sequence encoding the same;
• (c) selecting a protein or functional fragment thereof for enabling the metabolizing of the xenobiotic fuel and obtaining a nucleic acid sequence encoding the same;
• (d) providing (i) a vector comprising a promoter, the promoter operably linked to a nucleic acid encoding a transporter protein or a functional fragment thereof for transport of the xenobiotic fuel into the bioengineered cell, and a selective marker;
• and (ii) a vector comprising a promoter, the promoter operably linked to a nucleic acid encoding a protein or a functional fragment thereof for metabolizing the xenobiotic fuel in the bioengineered cell, and a selective marker;
• (e) isolating a cell of interest from a subject;
• (f) transfecting or transducing the cell of interest with (i) the vector comprising a nucleic acid encoding a transporter protein or a functional fragment thereof for transport of the xenobiotic fuel into the bioengineered cell;
• and (ii) the vector comprising a nucleic acid encoding a protein or a functional fragment thereof for enabling the metabolizing of the xenobiotic fuel in the bioengineered cell.