RADIOCONJUGATES TARGETING CD33 IN THE TREATMENT OF BREAST CANCER
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 breast cancer in a human subject, comprising
administering a therapeutically effective amount of 225 Ac-labeled lintuzumab or a 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to a human subject in need of treatment for a breast cancer.
2 . The method of claim 1 , wherein the breast cancer is metastatic breast cancer, tamoxifen-sensitive breast cancer, tamoxifen-resistant breast cancer or triple negative breast cancer (TNBC).
3 . The method of claim 2 , wherein the breast cancer is metastatic breast cancer.
4 . The method of claim 2 , wherein the breast cancer is tamoxifen-sensitive breast cancer, tamoxifen-resistant breast cancer.
5 . The method of claim 2 , wherein the breast cancer is tamoxifen-resistant breast cancer.
6 . The method of claim 2 , wherein the breast cancer is triple negative breast cancer (TNBC).
7 . The method of claim 1 , further comprising
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
8 . The method of claim 2 , further comprising
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
9 . The method of claim 3 , further comprising
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
10 . The method of claim 4 , further comprising
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
11 . The method of claim 5 , further comprising
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
12 . The method of claim 6 , further comprising
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
13 . The method of claim 1 , wherein the step of administering the therapeutically effective amount of 225 Ac-labeled lintuzumab or the 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to the human subject in need of treatment for the breast cancer comprises:
(i) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the human subject; or
(ii) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and the CD33-binding antibody fragment of lintuzumab to the subject.
14 . The method of claim 2 , wherein the step of administering the therapeutically effective amount of 225 Ac-labeled lintuzumab or the 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to the human subject in need of treatment for the breast cancer comprises:
(i) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the human subject; or
(ii) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and the CD33-binding antibody fragment of lintuzumab to the subject.
15 . The method of claim 7 , wherein the step of administering the therapeutically effective amount of 225 Ac-labeled lintuzumab or the 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to the human subject in need of treatment for the breast cancer comprises:
(i) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the human subject; or
(ii) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and the CD33-binding antibody fragment of lintuzumab to the subject.
16 . The method of claim 8 , wherein the step of administering the therapeutically effective amount of 225 Ac-labeled lintuzumab or the 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to the human subject in need of treatment for the breast cancer comprises:
(i) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the human subject; or
(ii) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and the CD33-binding antibody fragment of lintuzumab to the subject.
17 . A method for treating a solid tumor cancer in a human subject, comprising
administering a therapeutically effective amount of 225 Ac-labeled lintuzumab or a 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to a human subject in need of treatment for a solid tumor cancer,
wherein the solid tumor cancer is hepatocellular carcinoma (HCC), melanoma, non-small cell lung cancer (NSCLC), renal cancer, head and neck cancer, prostate cancer, colorectal cancer, pancreatic cancer, or glioblastoma.
18 . The method of claim 17 , wherein the step of administering the therapeutically effective amount of 225 Ac-labeled lintuzumab or the 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to the human subject in need of treatment for the breast cancer comprises:
(i) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the human subject; or
(ii) administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and the CD33-binding antibody fragment of lintuzumab to the subject.
19 . The method of claim 18 , wherein the step of administering the therapeutically effective amount of 225 Ac-labeled lintuzumab or the 225 Ac-labeled CD33-binding antibody fragment of lintuzumab to the human subject in need of treatment for the breast cancer comprises:
administering a 225 Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab to the human subject.
20 . The method of claim 17 , further comprising:
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
21 . The method of claim 18 , further comprising:
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.
22 . The method of claim 19 , further comprising:
administering to the subject a therapeutically effective amount of one or more of a PD-L1 inhibitor, a PD-1 inhibitor, and a CTLA-4 inhibitor.