Radioimmunoconjugates and uses thereof
The present invention relates to a radioimmunoconjugate that binds human CD37. Pharmaceutical compositions and uses thereof for the treatment of cancer—and in particular B-cell malignancies—are aspects of the present invention.
1. A radioimmunoconjugate that binds human CD37 comprising:
a) a murine monoclonal antibody HH1 comprising an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2 and the light chain comprises the amino acid sequence of SEQ ID NO: 4,
b) a chelating linker, and
c) a radionuclide selected from the group consisting of 177 Lu, 225 Ac, 227 Th, 212 Pb, and 90 Y.
2. The radioimmunoconjugate according to claim 1 , wherein the radionuclide is 177 Lu.
3. A pharmaceutical composition comprising the radioimmunoconjugate according to claim 1 , and a pharmaceutically acceptable carrier.
4. The pharmaceutical composition according to claim 3 , further comprising one or more additional antibodies or radioimmunoconjugates.
5. The pharmaceutical composition according to claim 4 , wherein the one or more additional antibodies or radioimmunoconjugates are specific for CD20.
6. A method of inhibiting a B-cell malignancy comprising:
providing the radioimmunoconjugate according to claim 1 to a subject in need thereof.
7. The method according to claim 6 , wherein said subject has non-Hodgkin lymphoma or chronic lymphocytic leukemia.
8. The method according to claim 6 , wherein the radioimmunoconjugate is administered in combination with or in addition to another therapy.
9. The method according to claim 8 , wherein the therapy is selected from the group consisting of chemotherapy, monoclonal antibody therapy, surgery, radiotherapy, and photodynamic therapy or a combination thereof.
10. The method according to claim 8 , wherein the therapy comprises administration of an anti-CD20 and/or anti-CD37 monoclonal antibody prior to the treatment with the radioimmunoconjugate.
11. A kit for the production of the radioimmunoconjugate according to claim 1 comprising two or more vials, wherein one vial contains a conjugate comprising a chelator linked to a murine monoclonal antibody HH1 comprising an immunoglobulin heavy chain and an immunoglobulin light chain wherein the immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 2 and the immunoglobulin light chain comprises the amino acid sequence of SEQ ID NO: 4; and a second vial contains a radionuclide.
12. The kit according to claim 11 , wherein the content of one or several of the vials are either lyophilized or in a solution.