Immunoconjugates, compositions for making them, and methods of making and use
An immunoconjugate in which a phosphate-prodrugged DNA minor groove binding agent of formula (I), where X is a nucleophilically displaceable leaving group, is conjugated to an antibody or an antigen binding fragment of an antibody, and compounds that can be used for making such immunoconjugates, and uses of such immunoconjugates.
1. A method for treating a cancer in a subject suffering from such cancer, comprising administering to the subject a therapeutically effective amount of an immunoconjugate having a structure according to formula (IIIa').
wherein
n is 1, 2, 3, 4, or 5; and
Ab represents a human monoclonal antibody that recognizes a human antigen selected from the group consisting of CD70, mesothelin, PSMA, CD19, glypican-3, and CD22;
or a pharmaceutically acceptable salt thereof;
and wherein the cancer is renal cancer, pancreatic cancer, ovarian cancer, lymphoma, colon cancer, mesothelioma, gastric cancer, lung cancer, prostate cancer, adenocarcinoma, liver cancer, or breast cancer.
2. A method according to claim 1 , wherein the cancer comprises cancer cells that express human CD70, mesothelin, PSMA, CD19, glypican-3, or CD22.
3. A method according to claim 1 , wherein the human antigen is CD70.
4. A method according to claim 1 , wherein the human antigen is mesothelin.
5. A method according to claim 1 , wherein the human antigen is PSMA.
6. A method according to claim 1 , wherein the human antigen is CD19.
7. A method according to claim 1 , wherein the human antigen is glypican-3.
8. A method according to claim 1 , wherein the human antigen is CD22.
9. A method according to claim 1 , wherein the cancer is renal cancer.
10. A method according to claim 1 , wherein the cancer is pancreatic cancer.
11. A method according to claim 1 , wherein the cancer is ovarian cancer.
12. A method according to claim 1 , wherein the cancer is lymphoma.
13. A method according to claim 1 , wherein the cancer is colon cancer.
14. A method according to claim 1 , wherein the cancer is mesothelioma.
15. A method according to claim 1 , wherein the cancer is gastric cancer.
16. A method according to claim 1 , wherein the cancer is lung cancer.
17. A method according to claim 1 , wherein the cancer is prostate cancer.
18. A method according to claim 1 , wherein the cancer is adenocarcinoma.
19. A method according to claim 1 , wherein the cancer is liver cancer.
20. A method according to claim 1 , wherein the cancer is breast cancer.