Anti-CD33 antibodies and use thereof for immunotargeting in treating CD33-associated illnesses
The invention relates to antibodies to the tumor-associated antigen CD33 and to the use thereof for immunotargeting CD33-positive cells. The antibodies according to the invention are suitable for use in the field of medicine, pharmaceuticals, and biomedical research. According to the invention, the aim is achieved by means of novel anti-CD33 antibodies comprising the complementary determining regions (CDRs) defined in the claim. The antibodies according to the invention are characterized by a high affinity for human CD33, of the order of magnitude of 10 −10 mol/l. The CDR sequences according to the invention are suitable in particular for producing recombinant fragments (such as scFv fragments or bispecific antibodies) and for immunotargeting, due to the high affinity thereof. The invention further relates to the use of an antibody according to the invention for producing a medication for therapeutic and/or diagnostic application for illnesses associated with the expression of CD33, particularly for acute myeloid leukemia (AML). The invention thus also comprises a pharmaceutical composition comprising one or more antibodies according to the invention in association with a pharmaceutically acceptable thinning agent or carrier.
1. An isolated monoclonal anti-CD33 antibody containing six complementary determining regions (CDRs), characterized in that the six CDRs comprise the following sequences:
a) variable region of heavy chain (V H )
CDR1 DYVVH (SEQ ID No. 1),
CDR2 YINPYNDGTKYNEKFKG (SEQ ID No. 2),
CDR3 DYRYEVYGMDY (SEQ ID No. 3),
and
b) variable region of light chain (V L )
CDR1 TASSSVNYIH (SEQ ID No. 4),
CDR2 TSKVAS (SEQ ID No. 5),
CDR3 QQWRSYPLT (SEQ ID No. 6).
2. The antibody according to claim 1 , containing the following structure:
a heavy chain variable region with the sequence of SEQ ID NO. 13
and a light chain variable region with a sequence of SEQ ID NO. 14.
3. The antibody according to claim 1 , containing additionally at least one of the following structures
a constant region of a heavy chain of a human IgG,
a constant region (C L ) of the human kappa light chain
and/or
a human IgG3 hinge region,
optionally in the form of a F(ab′) 2 fragment.
4. The antibody according to claim 1 in the form of an scFv fragment or in the form of a F(ab′) 2 fragment.
5. The antibody according to claim 1 , characterized in that it is conjugated with an effector group or a further antibody or antigen binding fragment that is specific to another antigen than CD33.
6. The antibody according to claim 5 , wherein the effector group is selected from toxins, enzymes, co-stimulating molecules, radionuclides and nucleic acids.
7. The antibody according to claim 1 , characterized in that it is conjugated with a ligand that binds specifically to effector cells and in this way affects their activity.
8. An isolated nucleic acid coding for an antibody of claim 1 .
9. A vector containing a nucleic acid sequence of claim 8 .
10. An isolated host cell containing a nucleic acid of claim 8 or a vector containing a nucleic acid of claim 8 .
11. A pharmaceutical composition, containing an antibody of claim 1 in association with a pharmaceutically acceptable dilution agent or carrier.
12. A method for preparing an antibody of claim 1 , in which:
a. an isolated host cell that contains a nucleic acid coding for an antibody of claim 1 or that contains a vector containing a nucleic acid coding for an antibody of claim 1 is exposed to conditions under which an expression and optionally a secretion of the antibody takes place, and
b. the antibody is at least partially purified.
13. The antibody according to claim 1 wherein the antibody is a humanized antibody.
14. The antibody according to claim 5 , wherein the connection of the antibody to the effector group is prepared by the expression as a fusion protein.