Pyrrolobenzodiazepine-antibody conjugates
Conjugates of an antibody that binds to CD25 with PBD dimers.
1. A method of treating a CD25-expressing cancer comprising administering to a patient a therapeutically-acceptable amount of a conjugate of formula ConjA:
where Ab is an antibody that binds to CD25 and comprises a VH domain comprising a VH CDR1 with the amino acid sequence of SEQ ID NO.3, a VH CDR2 with the amino acid sequence of SEQ ID NO.4, and a VH CDR3 with the amino acid sequence of SEQ ID NO.5; and a VL domain comprising a VL CDR1 with the amino acid sequence of SEQ ID NO.6, a VL CDR2 with the amino acid sequence of SEQ ID NO.7, and a VL CDR3 with the amino acid sequence of SEQ ID NO.8,
wherein the drug loading is from 1 to about 8; and the patient is administered a chemotherapeutic agent in combination with the conjugate; and
wherein the chemotherapeutic agent is an antimetabolite or a further antibody.
2. The method according to claim 1 , wherein the antibody comprises a VH domain having the amino acid sequence according to SEQ ID NO. 1.
3. The method according to claim 1 , wherein the antibody comprises a VL domain having the amino acid sequence according to SEQ ID NO. 2.
4. The method according to claim 1 , wherein the antibody is an intact antibody.
5. The method according to claim 1 , wherein the antibody is humanized, deimmunized, or resurfaced.
6. The method according to claim 1 , wherein the antibody is a fully human monoclonal IgG1 antibody.
7. The conjugate according to claim 6 , wherein the antibody is IgG1,κ.
8. The method according to claim 1 , wherein the drug loading is 1, 2, 3, or 4.
9. The method according to claim 1 , wherein the conjugate is ConjE.
10. The method according to claim 1 , wherein the CD25-expressing cancer is lymphoma.
11. The method according to claim 1 , wherein the CD25-expressing cancer is leukemia.
12. The method according to claim 11 , wherein the leukemia is Acute Lymphoblastic Leukemia (ALL).
13. A method of treating a CD25-expressing cancer comprising administering to a patient a therapeutically-acceptable amount of a conjugate of formula ConjE:
where Ab is an antibody that binds to CD25 and comprises: a VH domain comprising a VH CDR1 with the amino acid sequence of SEQ ID NO.3, a VH CDR2 with the amino acid sequence of SEQ ID NO.4, and a VH CDR3 with the amino acid sequence of SEQ ID NO.5; and a VL domain comprising a VL CDR1 with the amino acid sequence of SEQ ID NO.6, a VL CDR2 with the amino acid sequence of SEQ ID NO.7, and a VL CDR3 with the amino acid sequence of SEQ ID NO.8,
wherein the drug loading is from 1 to about 8; and the patient is administered a chemotherapeutic agent in combination with the conjugate;
wherein the chemotherapeutic agent is an antimetabolite or a further antibody.