Polyspecific binding molecules and uses thereof
AssigneeAltor BioScience Corporation
InventorsJon A. Weidanz, Kimberlyn F. Card, Linda A. Sherman, Norman R. Klinman, Hing C. Wong
Life of this patent
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Abstract
The present invention relates to polyspecific binding molecules and particularly single-chain polyspecific binding molecules that include at least one single-chain T-cell receptor (sc-TCR) covalently linked through a peptide linker sequence to at least one single-chain antibody (sc-Ab). Further disclosed are methods and compositions for testing and using the molecules.
Claims47
A single-chain polyspecific binding protein comprising at least one single-chain T-cell receptor (sc-TCR) or functional fragment thereof covalently linked through a first peptide linker sequence to at least one single-chain antibody (sc-Ab) or functional fragment thereof.
A single-chain polyspecific binding protein comprising covalently linked in sequence:
- 1) a sc-TCR or functional fragment thereof, 2) a first polypeptide linker sequence, and 3) a single-chain antibody or functional fragment thereof.
A kit comprising at least one of a single-chain polyspecific binding protein and a polynucleotide encoding the protein.
A method for making a single-chain polyspecific binding protein comprising at least one single-chain T-cell receptor (sc-TCR) or functional fragment thereof and at least one single-chain Fv (sc-Fv) or functional fragment thereof, the method comprising:
- a) introducing into a host cell a DNA vector encoding a single-chain polyspecific binding protein of interest,
- b) culturing the host cell in media under conditions sufficient to express the single-chain polyspecific binding protein in the cell or the media;
- and
- c) purifying the single-chain polyspecific binding protein from the hydridoma cells or media.
A method for killing a target cell comprising an major histocompatibility complex (MHC) or human-leukocyte-associated antigen (HLA), the method comprising:
- a) contacting a plurality of cells with a single-chain polyspecific binding protein comprising at least one single-chain T-cell receptor (sc-TCR) or functional fragment thereof and at least one single-chain Fv (sc-Fv) or functional fragment thereof, wherein the plurality of cells further comprises immune cells and the target cells comprising the MHC,
- b) forming a specific binding complex (bridge) between the MHC on the target cells and an activation molecule (marker) on the immune cells sufficient to activate the immune cells;
- and
- c) killing the target cells with the activated immune cells.
A method for preventing or treating a cancer in a patient in which the cancer features pHLA-expressing tumor cells, the method comprising:
- a) administering to the patient a single-chain polyspecific binding protein comprising at least one single-chain T-Cell receptor (sc-TCR) or functional fragment thereof and at least one single-chain antibody or functional fragment thereof;
- b) forming a specific binding complex (bridge) between the pHLA-expressing tumor cells and immune cells sufficient to activate the immune cells;
- and
- c) damaging or killing the tumor cells sufficient to prevent or treat the cancer in the patient.
Dependencies are inferred from the claim text.