CD33 Radioconjugates for MDSC Depletion in Sarcoma Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Myeloid-derived suppressor cells (MDSCs), which are CD33-positive, contribute to immunosuppression and immunological escape in solid tumors and other cancers, and are difficult to target effectively with existing treatments.
Innovation Solution
The use of radioconjugates, such as Actinium-225 labeled monoclonal antibodies against CD33, in combination with other cancer-associated targets like DR5, 5T4, HER2, or HER3, along with antibody drug conjugates and immune checkpoint inhibitors, to selectively target and deplete MDSCs and enhance the immune response against cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If radioconjugates targeting CD33 are used to deplete MDSCs, then the immune response against solid tumors is enhanced, but the device complexity and treatment protocol complexity increase
Solution Approach 1:
The treatment protocol is segmented into distinct phases: administration of radioconjugate, followed by optional administration of antibody drug conjugates or immune checkpoint inhibitors. This segmentation allows the complex treatment to be broken down into manageable steps that can be administered sequentially, reducing the perceived complexity while maintaining the enhanced immune response benefit
Solution Approach 2:
The radioconjugate targeting CD33 serves multiple functions: it selectively binds to MDSCs, delivers radiation to deplete them, and can be combined with other therapeutic agents (antibody drug conjugates or immune checkpoint inhibitors) to create a multi-functional treatment platform that addresses both immunosuppression and tumor growth
2Reliability
If combination therapy with multiple cancer-associated targets is used, then therapeutic efficacy is improved, but the device complexity and treatment cost increase
Solution Approach 1:
The patent merges multiple therapeutic approaches into a single combination therapy protocol: radioconjugate targeting CD33 is combined with either antibody drug conjugates or immune checkpoint inhibitors. This merging allows the synergistic effects of different mechanisms to be achieved while managing complexity through coordinated administration rather than separate independent treatments
Solution Approach 2:
The radioconjugate is administered first to deplete MDSCs and reduce immunosuppression before administering antibody drug conjugates or immune checkpoint inhibitors. This preliminary action prepares the immune system to respond more effectively to subsequent therapies, improving overall efficacy while simplifying the treatment sequence
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Significantly depletes MDSCs, thereby enhancing the immune response against solid tumors and other cancers, including hematological malignancies, and provides therapeutic benefits for conditions like haemophagocytic lymphohistiocytosis and macrophage activation syndrome.
Implementation Method 1
Actinium-225 labeled monoclonal antibodies against CD33
Data Source
AI summary
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 DRS, 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.