Radioconjugates targeting CD33 in the treatment of cancers
The invention provides compositions and methods for treating cancers and proliferative disorders, including solid tumor cancers and non-myeloid hematological malignancies, using radioconjugates targeting CD33, alone or in combination with one or more radioconjugates targeting other cancer-associated targets such as DR5, 5T4, HER2, HER3, and TROP2, antibody drug conjugates targeting these or other cancer-associated targets, therapeutic antibodies targeting these or other cancer-associated targets, chemotherapy agents and regimens, and immune checkpoint inhibitors.
1 . A method for treating a solid tumor cancer or solid tumor premalignancy in a mammalian subject not afflicted with a myeloid-derived hematological cancer or myeloid-derived hematological premalignancy, comprising:
administering a therapeutically effective amount of a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the mammalian subject.
2 . The method of claim 1 , wherein the solid tumor cancer or solid tumor premalignancy comprises ovarian cancer, non-small cell lung carcinoma, head and neck squamous cell cancer, pancreatic cancer, renal cancer, breast cancer, metastatic breast cancer, tamoxifen-sensitive tamoxifen-resistant breast cancer, triple negative breast cancer, prostate cancer, castration-resistant prostate cancer (CRPC), pancreatic cancer, small cell lung carcinoma (SCLC), non-small cell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), cholangiocarcinoma, gastric cancer, colorectal cancer, esophageal cancer, or Barrett's esophagus.
3 . The method of claim 2 , wherein the mammalian subject is a human patient.
4 . The method of claim 3 , wherein the human patient is afflicted with a solid tumor cancer.
5 . The method of claim 1 , further comprising
administering at least one immune checkpoint inhibitor to the mammalian subject.
6 . The method of claim 5 , wherein the at least one immune checkpoint inhibitor comprises one or both of a PD-1 and PD-L1 inhibitor.
7 . The method of claim 6 , wherein the mammalian subject is a human patient.
8 . The method of claim 7 , wherein the human patient is afflicted with a solid tumor cancer.
9 . The method of claim 5 , wherein the at least one immune checkpoint inhibitor comprises a CTLA-4 inhibitor.
10 . The method of claim 9 , wherein the mammalian subject is a human patient.
11 . The method of claim 10 , wherein the human patient is afflicted with a solid tumor cancer.
12 . The method of claim 5 , wherein the mammalian subject is a human patient.
13 . The method of claim 12 , wherein the human patient is afflicted with a solid tumor cancer.
14 . The method of claim 1 , wherein the solid tumor cancer or solid tumor premalignancy is a CD33 low-expressing or CD33-negative solid tumor cancer or CD33 low-expressing or CD33-negative solid tumor premalignancy.
15 . The method of claim 14 , wherein the mammalian subject is a human patient.
16 . The method of claim 15 , wherein the human patient is afflicted with a solid tumor cancer.
17 . The method of claim 1 , wherein the mammalian subject is a human patient.
18 . The method of claim 17 , wherein the human patient is afflicted with a solid tumor cancer.