Method for the treatment or prophylaxis of cancer by targeting the extracellular portion of keratin 14 (KRT14) residing on cancer cells
AssigneeHudson Institute of Medical Research
InventorsAndrew Nicholas Stephens, Maree Bilandzic
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Abstract
Disclosed herein are methods, uses and compositions for the treatment or prophylaxis of cancer in a mammalian subject comprising administering to the subject an amount of an agent which targets an extracellular portion of KRT14 or its functional homolog or variant thereof resident on cancer cells or an agent which induces production of an antagonist of the extracellular portion of KRT14 or its functional homolog or variant on cancer cells. The present disclosure also extends to methods of monitoring and/or diagnosing cancer in a subject.
Claims15
A method for the treatment of a keratin-14 (KRT14)-positive cancer in a mammalian subject, said method comprising administering to said subject an amount of an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells,
- wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8;
- and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:
- 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11, the amount effective to prevent or reduce cancer cell invasion, migration and/or metastasis, thereby treating the KRT14-positive cancer in the subject.
A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells,
- wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8;
- and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:
- 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11, and
- wherein said antibody or antigen-binding fragment thereof directly induces cytotoxicity or cytostasis of the cancer cells.
A diagnostic reagent comprising an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells,
- wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8;
- and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:
- 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11, and
- wherein the antibody or antigen-binding fragment thereof is conjugated to a reporter molecule.
A method for detecting circulating KRT14-positive cancer cells in a patient, the method comprising:
- (a) providing a blood sample from the patient;
- (b) contacting the blood sample with an antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells, wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8;
- and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:
- 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11 to determine the presence of KRT14 positive cancer cells in the sample.
An antibody or antigen-binding fragment thereof that binds specifically to an extracellular portion of keratin-14 (KRT14) on cancer cells, wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH comprises a complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO:6, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:7 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:8;
- and wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:9, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:
- 10, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:11.
Dependencies are inferred from the claim text.