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AssigneeVyGen-Bio, Inc.
InventorsArnika WAGNER, Evren ALICI
Estimating the term…
The method entails modification of non-malignant cells for transplantation or therapy to avoid recognition and attack by monoclonal antibodies and antibody-derived therapeutics. Many therapies that use monoclonal antibodies or antibody-derived therapeutics not only bind to the intended target epitope on malignant cells, but also to the same target epitope on healthy non-malignant cells that express the target antigen. This phenomenon is termed on-target off-tumor effect. This can cause rejection, immune cell attack or opsonization of non-malignant cells, which in turn can cause severe side effects which often hampers the therapeutic effect. Similarly, cytokines in cytokine therapy can bind to receptors on bystander cells and cause unintended effects. The methods of the present invention change the antigen epitope or the cytokine receptor on non-malignant and bystander cells for adoptive cell therapy, thereby disrupting the binding of the therapeutic agent—antibody or cytokine—to the target antigen or receptor on non-malignant cells.
A cell comprising an otherwise wild-type protein having at least one mutation in the binding site of a therapeutic agent, the at least one mutation being configured to disrupt specific binding of the therapeutic agent to the protein while retaining the physiological function of the wild-type protein.
The cell of claim any of the preceding claims which is allogeneic and/or otherwise configured for adoptive therapy in a subject, preferably a human subject.
The cell of claim any of the preceding claims wherein the therapeutic agent binding site is present in a protein expressed on the surface of the cell, the protein selected from CD38, SLAMF7, CD19, CD20, CD22, CD25, CD28, CD30, CD33, CD47, CD52, or PDGFRA.
A method of treating a patient comprising administering to the patient:
A cell configured for adoptive therapy, which comprises a cell surface and/or transmembrane protein having at least one mutation in the binding site of a therapeutic antibody, the at least one mutation being configured to disrupt specific binding of the therapeutic antibody to the cell surface and/or transmembrane protein.
A therapy cell comprising at least one mutation to more than one therapeutic antibody target site such that the therapeutic antibodies no longer bind to the cell.
A cell comprising an exogenous nucleotide sequence which encodes a mutant form of a human cell-surface or transmembrane protein, the mutant form engineered to lack an epitope that allows for specific binding to a therapeutic antibody but otherwise having all the same functional capabilities as the corresponding wild-type cell-surface or transmembrane protein.
A method of producing a cell for adoptive therapy comprising:
Dependencies are inferred from the claim text.