Means and methods for counteracting myeloproliferative or lymphoproliferative disorders
The invention provides human AML-specific binding compounds that are able to bind a cell surface component of AML cells. Therapeutic uses of binding compounds against AML are also provided.
1. A synthetic or recombinant nucleic acid molecule or functional equivalent thereof, comprising:
a sequence encoding the heavy chain CDR1 sequence of SEQ ID NO: 209, and
a sequence encoding the heavy chain CDR2 sequence of SEQ ID NO: 213, and
a sequence encoding the heavy chain CDR3 sequence of SEQ ID NO: 217, and
a sequence encoding the light chain CDR1 sequence of SEQ ID NO: 221, and
a sequence encoding the light chain CDR2 sequence of SEQ ID NO: 225, and
a sequence encoding the light chain CDR3 sequence of SEQ ID NO: 229.
2. The synthetic or recombinant nucleic acid molecule or functional equivalent of claim 1 comprising:
a heavy chain CDR1 encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 241, and
a heavy chain CDR2 encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 245, and
a heavy chain CDR3 encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 249, and
a light chain CDR1 encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 253, and
a light chain CDR2 encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 257, and
a light chain CDR3 encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 261.
3. The synthetic or recombinant nucleic acid molecule or functional equivalent of claim 1 comprising:
a heavy chain encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 265, and/or
a light chain encoding nucleic acid sequence which has at least 90% sequence identity to SEQ ID NO: 269.
4. The nucleic acid molecule or functional equivalent of claim 1 , comprising cDNA, peptide nucleic acid (PNA), locked nucleic acid (LNA), or a DNA/RNA helix.
5. The nucleic acid molecule or functional equivalent of claim 1 , wherein the nucleic acid molecule or functional equivalent is codon-optimized for a non-human expression system.
6. A vector comprising:
a nucleic acid sequence or functional equivalent thereof encoding the heavy chain CDR1 sequence of SEQ ID NO: 209, and
a nucleic acid sequence or functional equivalent thereof encoding the heavy chain CDR2 sequence of SEQ ID NO: 213, and
a nucleic acid sequence or functional equivalent thereof encoding the heavy chain CDR3 sequence of SEQ ID NO: 217, and
a nucleic acid sequence or functional equivalent thereof encoding the light chain CDR1 sequence of SEQ ID NO: 221, and
a nucleic acid sequence or functional equivalent thereof encoding the light chain CDR2 sequence of SEQ ID NO: 225, and
a nucleic acid sequence or functional equivalent thereof encoding the light chain CDR3 sequence of SEQ ID NO: 229.
7. The vector of claim 6 , comprising a nucleic acid sequence encoding the VH and/or VL of antibody AT14-013.
8. The vector of claim 6 , wherein the vector is a retroviral or lentiviral vector.
9. A composition comprising one or more nucleic acid molecules or functional equivalents thereof, comprising:
a sequence encoding the heavy chain CDR1 sequence of SEQ ID NO: 209, and
a sequence encoding the heavy chain CDR2 sequence of SEQ ID NO: 213, and
a sequence encoding the heavy chain CDR3 sequence of SEQ ID NO: 217, and
a sequence encoding the light chain CDR1 sequence of SEQ ID NO: 221, and
a sequence encoding the light chain CDR2 sequence of SEQ ID NO: 225, and
a sequence encoding the light chain CDR3 sequence of SEQ ID NO: 229.
10. The composition of claim 9 , wherein the composition is a pharmaceutical composition which comprises a pharmaceutically acceptable carrier, diluent or excipient.
11. The composition of claim 9 , wherein the composition is for use as a medicament or prophylactic agent.
12. The composition of claim 9 , wherein the composition is for use in a method for at least in part treating or preventing a myeloproliferative or lymphoproliferative disorder.
13. The composition of claim 9 , wherein the composition is for use in diagnosis of a myeloproliferative or lymphoproliferative disorder.
14. The composition of claim 13 , wherein the myeloproliferative disorder is acute myeloid leukemia (AML).
15. The composition of claim 13 , wherein the lymphoproliferative disorder is lymphoma, B non-Hodgkin lymphoma or multiple myeloma.
16. A host cell comprising one or more nucleic acid molecules or functional equivalents thereof, comprising:
a sequence encoding the heavy chain CDR1 sequence of SEQ ID NO: 209, and
a sequence encoding the heavy chain CDR2 sequence of SEQ ID NO: 213, and
a sequence encoding the heavy chain CDR3 sequence of SEQ ID NO: 217, and
a sequence encoding the light chain CDR1 sequence of SEQ ID NO: 221, and
a sequence encoding the light chain CDR2 sequence of SEQ ID NO: 225, and
a sequence encoding the light chain CDR3 sequence of SEQ ID NO: 229.