Compositions and methods to reduce therapeutic t cell toxicity
AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorsMarco L. Davila, Gongbo Li
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AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorsMarco L. Davila, Gongbo Li
Estimating the term…
Disclosed are off-the-shelf immune effector cells that are engineered to express anti-CD3 antibodies disclosed herein that are configured to autoactivate the immune effector cells, thereby decreasing expression of T cell receptors (e.g. TCRαβ) that could result in GVHD. Also disclosed are methods for modifying donor immune effector cells to make them suitable for off-the-shelf treatment of allogeneic subjects. These methods involve engineering the cells to express an anti-CD3 antibody configured to activate the cells. In some embodiments, the antibody is a bi-specific antibody that binds the CD3 complex on the immune effector cells. In other embodiments, the antibody is a membrane bound anti-CD3 antibody that autoactivates the immune effector cell.
A method for treating cancer in a subject, comprising obtaining immune effector cells from an allogeneic donor;
The method of claim 1, wherein the antibody is a bi-specific antibody.
The method of any one of claims 1 to 4, wherein the immune effector cells are further engineered to express a chimeric antigen receptor (CAR).
The method of any one of claims 1 to 5, wherein the immune effector cell is selected from the group consisting of an αβT cell, γδT cell, a Natural Killer (NK) cells, a Natural Killer T (NKT) cell, a B cell, an innate lymphoid cell (ILC), a cytokine induced killer (CIK) cell, a cytotoxic T lymphocyte (CTL), a lymphokine activated killer (LAK) cell, a regulatory T cell, or any combination thereof.
A method for enhancing CAR-T cells for allogeneic cell transfer, comprising engineering the CAR-T cells to secrete a monospecific anti-CD3 antibody.
The method of claim 7, wherein the monospecific anti-CD3 antibody is a single chain variable fragment (scFv).
A CAR-T cell engineered to express a monospecific anti-CD3 antibody.
A method for enhancing immune effector cells for allogeneic cell transfer, comprising
Dependencies are inferred from the claim text.