Anti-cancer antibodies, combination therapies, and uses thereof
Inventors
Assignees
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Publication Number
US-11279768-B1
Publication Date
2022-03-22
Expiration Date
Abstract
This invention relates to antibodies to anti-cancer antibodies and uses thereof, including combination therapies and compositions. Combinations targeting the extrinsic, intrinsic, or common pro-apoptotic pathways are provided. Exemplary anti-cancer antibodies are differentially expressed in cancers, such as antibodies targeting the bind the antigens NPC-1, 16C3, or 31.1. Exemplary anti-cancer antibodies target lung cancer, ovarian cancer, cervical cancer, uterine cancer, pancreas cancer, breast cancer, and colon cancer.
Core Innovation
The invention describes anti-cancer treatment using an anti-CAA antibody that is specific for a cancer-associated antigen, including a NEO-201 antibody that comprises defined light chain variable region CDRs and defined heavy chain variable region CDRs. The anti-CAA antibody targets a cancer that expresses an antigen specifically bound by the anti-CAA antibody, where the cancer-associated antigen is 16C3.
A central aspect of the invention is administering the anti-CAA antibody together with a second therapeutic agent at a lower dosage than the effective dosage of the anti-CAA antibody or the second therapeutic agent when administered individually. The combined regimen is associated with enhanced therapeutic efficacy, including a synergistic effect, and dependent claims refine the second therapeutic agent and the performance of the combination relative to individual administration.
The invention also frames cancer cell killing in terms of apoptosis-pathway involvement, including extrinsic apoptosis pathway, intrinsic apoptosis pathway, and common apoptosis pathway, with apoptotic caspase involvement including caspase-8 versus caspase-3 and caspase-3/7 assay. It additionally describes radiolabeled antibody localization and imaging in vivo, and antigen expression assessment using flow cytometry and immunohistochemistry.
Claims Coverage
The independent claim covers a combination cancer-treatment method using a specific anti-CAA antibody, NEO-201 against 16C3, together with a second therapeutic agent, with both agents administered at lower dosages than individual effective dosages. The coverage includes inventive refinements in dependent claims such as enhanced therapeutic efficacy compared with individual administration, selection of the second agent as death-receptor pathway targeting or intrinsic apoptosis/Bcl-2-family targeting, and an apoptosis outcome limitation.
Lower-dosage combination cancer treatment with anti-CAA antibody
A method of treatment comprising administering to a subject an effective amount of an antibody specific for a cancer-associated antigen (anti-CAA antibody) where the cancer-associated antigen is 16C3, together with a second therapeutic agent, with the anti-CAA antibody and the second therapeutic agent administered at a lower dosage than the effective dosage of either when administered individually, wherein the method is for the treatment of a cancer that expresses an antigen specifically bound by the anti-CAA antibody.
NeO-201 anti-CAA antibody defined by CDR composition
The method where the anti-CAA antibody comprises a NEO-201 antibody comprising a light chain variable region containing the CDR1 of SEQ ID NO: 77 or 97, CDR2 of SEQ ID NO: 78 or 98, and CDR3 of SEQ ID NO: 79 or 99, and comprising a heavy chain variable region containing the CDR1 of SEQ ID NO: 82 or 102, CDR2 of SEQ ID NO: 83 or 103, and CDR3 of SEQ ID NO: 84 or 104.
Enhanced therapeutic efficacy versus individual administration
The method further characterized such that the combination of said anti-CAA antibody with said second therapeutic agent provides enhanced therapeutic efficacy compared with administering the anti-CAA antibody and the second therapeutic agent individually.
Death-receptor pathway targeting second therapeutic agent
The method where the second therapeutic agent is a death-receptor-targeting agent including specific death ligands, receptors, or modulators, including gemcitabine, cisplatin, TRAIL, Fas ligand, TNFR1, TRAIL-R2, DR4, DR5, or CD95, or an agent that activates a death receptor or sensitizes the death receptor to activation by another agent.
Intrinsic apoptosis pathway / Bcl-2-family targeting second therapeutic agent
The method where the second therapeutic agent includes intrinsic-apoptosis and/or Bcl-2-family targeting activities, including proapoptotic and/or antiapoptotic Bcl-2 family members and named modulators or agents.
Apoptosis of cancer cells outcome limitation
The method characterized by causing apoptosis of cancer cells in the subject.
Overall, the claim coverage centers on a lower-dosage combination treatment using an anti-CAA antibody that is a NEO-201 antibody with specified CDR sequences against 16C3, combined with a second therapeutic agent selected for apoptosis-pathway effects. Dependent claims further emphasize enhanced therapeutic efficacy relative to individual dosing, and narrow the second agent toward death-receptor targeting or intrinsic apoptosis/Bcl-2-family targeting, with an apoptosis outcome limitation.
Stated Advantages
Enhanced therapeutic efficacy compared with administering the anti-CAA antibody and the second therapeutic agent individually.
Administering the anti-CAA antibody and the second therapeutic agent at a lower dosage than the effective dosage of either agent when administered individually.
Documented Applications
Cancer diagnostics and therapies using the described anti-CAA antibodies, including antigen expression assessment using flow cytometry and immunohistochemistry.
In vivo localization and imaging using a radiolabeled antibody, including described radiolabeled antibody imaging contexts.
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