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. An antibody, or a functional part thereof,
wherein said functional part thereof is defined as a single chain variable fragment (scFv), a Fab fragment or a F(ab′)2 fragment;
wherein said antibody or functional part is able to bind a cell surface component of acute myeloid leukemia (AML) cells, comprising:
a heavy chain CDR1 sequence comprising SEQ ID NO: 209;
a heavy chain CDR2 sequence comprising SEQ ID NO: 213;
a heavy chain CDR3 sequence comprising SEQ ID NO: 217;
a light chain CDR1 sequence comprising SEQ ID NO: 221;
a light chain CDR2 sequence comprising SEQ ID NO: 225; and
a light chain CDR3 sequence comprising SEQ ID NO: 229; and
wherein said antibody is, synthetic or recombinant; and
wherein said antibody or functional part is coupled to a detectable label, a chemotherapeutic drug, a toxic moiety, a CD3-specific binding compound, another AML-specific binding compound, or a radioactive compound.
2. The antibody or functional part according to claim 1 , comprising a variable heavy chain sequence having at least 95% sequence identity with a sequence selected from the group consisting of SEQ ID NO: 233.
3. The antibody or functional part according to claim 1 , comprising a variable light chain sequence having at least 95% sequence identity with a sequence selected from the group consisting of SEQ ID NO: 237.
4. A composition comprising:
an antibody or functional part, wherein said functional part is defined as a single chain variable fragment (scFv), a Fab fragment or a F(ab′)2 fragment; and wherein said antibody or functional part is able to bind a cell surface component of acute myeloid leukemia (AML) cells, comprising:
a heavy chain CDR1 sequence comprising SEQ ID NO: 209;
a heavy chain CDR2 sequence comprising SEQ ID NO: 213;
a heavy chain CDR3 sequence comprising SEQ ID NO: 217;
a light chain CDR1 sequence comprising SEQ ID NO: 221;
a light chain CDR2 sequence comprising SEQ ID NO: 225; and
a light chain CDR3 sequence comprising SEQ ID NO: 229; and wherein said antibody or functional part is coupled to a detectable label, a chemotherapeutic drug, a toxic moiety, a CD3-specific binding compound, another AML-specific binding compound, or a radioactive compound.
5. The composition according to claim 4 , wherein said composition is a pharmaceutical composition which comprises a pharmaceutically acceptable carrier, diluent or excipient.
6. The composition according to claim 5 , comprising at least two antibodies, or functional parts.
7. The composition according to claim 5 , wherein said composition is for use as a medicament.
8. The composition according to claim 5 , wherein said composition is for use in a method for at least in part treating a myeloproliferative or lymphoproliferative disorder.
9. The composition according to claim 5 , wherein said composition is for use in diagnosis of a myeloproliferative or lymphoproliferative disorder.
10. The composition according to claim 9 , wherein said myeloproliferative disorder is acute myeloid leukemia (AML).
11. The composition according to claim 9 , wherein said lymphoproliferative disorder is lymphoma, B-non-Hodgkin lymphoma or multiple myeloma.
12. The composition according to claim 4 , wherein said composition is used for determining whether a sample comprises myeloproliferative or lymphoproliferative cells.
13. A bispecific or multispecific binding compound that is able to bind a cell surface component of acute myeloid leukemia (AML) cells, comprising:
an antibody or a functional part thereof, wherein said functional part thereof is defined as a single chain variable fragment (scFv), a Fab fragment or a F(ab′)2 fragment, wherein said antibody or functional part is able to bind a cell surface component of acute myeloid leukemia (AML) cells, comprising a heavy chain CDR1 sequence comprising SEQ ID NO: 209 and a heavy chain CDR2 sequence comprising SEQ ID NO: 213 and a heavy chain CDR3 sequence comprising SEQ ID NO: 217 and a light chain CDR1 sequence comprising SEQ ID NO: 221 and a light chain CDR2 sequence comprising SEQ ID NO: 225 and a light chain CDR3 sequence comprising SEQ ID NO: 229; and
an immunomodulatory molecule.
14. A synthetic or recombinant antibody or immunoglobulin that is able to bind a cell surface component of acute myeloid leukemia (AML) cells, comprising:
one Fab fragment comprising a heavy chain CDR1 sequence comprising SEQ ID NO: 209 and a heavy chain CDR2 sequence comprising SEQ ID NO: 213 and a heavy chain CDR3 sequence comprising SEQ ID NO: 217 and a light chain CDR1 sequence comprising SEQ ID NO: 221 and a light chain CDR2 sequence comprising SEQ ID NO: 225 and a light chain CDR3 sequence comprising SEQ ID NO: 229; and
one Fab fragment of another antibody.
15. A chimeric antigen receptor (CAR) T cell that is able to bind a cell surface component of acute myeloid leukemia (AML) cells, said CAR comprising:
a heavy chain CDR1 sequence comprising SEQ ID NO: 209;
a heavy chain CDR2 sequence comprising SEQ ID NO: 213;
a heavy chain CDR3 sequence comprising SEQ ID NO: 217;
a light chain CDR1 sequence comprising SEQ ID NO: 221;
a light chain CDR2 sequence comprising SEQ ID NO: 225; and
a light chain CDR3 sequence comprising SEQ ID NO: 229.
16. The bispecific or multispecific binding compound according to claim 13 , wherein said immunomodulatory molecule is a CD3-specific binding compound.