Methods of treatment using anti-erbb antibody-maytansinoid conjugates
The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anri-ErbB receptor antibody-maytansinoid conjugates.
1. An immunoconjugate comprising an anti-ErbB2 antibody conjugated to a maytansinoid, wherein the antibody is huMAb4D5-8.
2. The immunoconjugate of claim 1 , wherein the maytansinoid is DM1 having the structure:
and wherein the antibody is chemically linked to the maytansinoid via a disulfide or thioether group at “R” shown in the structure.
3. The immunoconjugate of claim 1 , wherein the immunoconjugate comprises from 3 to 5 maytansinoid molecules per antibody molecule.
4. The immunoconjugate of claim 1 , wherein the antibody and the maytansinoid are conjugated by a chemical linker selected from N-succinimidyl-3-(2-pyridyldithio) propionate, N-succinimidyl-4-(2-pyridylthio)pentanoate (SPP) and succinimidyl-4-(N-maleimidomethyl)cyclohexanel-1-carboxylate.
5. A pharmaceutical composition comprising an immunoconjugate of any of claims 1 to 4 , and a pharmaceutically acceptable carrier.
6. The immunoconjugate of claim 4 , wherein the antibody and the maytansinoid are conjugated by succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate.
7. The immunoconjugate of claim 2 , wherein the antibody and the maytansinoid are conjugated by a chemical linker selected from N-succinimidyl-3-(2-pyridyldithio)propionate, N-succinimidyl-4-(2-pyridylthio)pentanoate (SPP) and succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate.
8. The immunoconjugate of claim 7 , wherein the antibody and the maytansinoid are conjugated by succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate.