TROP-2 ADC Combination Therapy with Immune Checkpoint Blockade
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Solution Overview
Problem
There is a need for novel therapies and combinations to treat Trop-2 expressing or tumor antigen positive cancers, as existing treatments like antibody drug conjugates and immune checkpoint inhibitors have limitations in efficacy.
Innovation Solution
Combination therapy involving a TROP-2-targeted antibody-drug conjugate (ADC) with an anti-PD-(L)1 antibody, optionally with an anti-TIGIT antibody, to treat Trop-2 positive cancers, and a tumor antigen-targeted antibody-drug conjugate (ADC) with a topoisomerase I inhibitor and an anti-PD-(L)1 antibody, optionally with an anti-TIGIT antibody, to treat tumor antigen positive cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monotherapy with antibody drug conjugate or immune checkpoint inhibitor is used, then treatment simplicity is maintained, but treatment efficacy is insufficient
Solution Approach 1:
The patent combines multiple therapeutic agents (antibody drug conjugate with immune checkpoint inhibitor, and optionally TIGIT inhibitor) into a unified treatment regimen. This merging of mechanisms of action targets both direct tumor cell killing and immune system activation, thereby improving treatment efficacy while managing the complexity through a coordinated combination rather than multiple separate therapies
2Reliability
If combination therapy with multiple agents is used, then treatment efficacy is improved, but treatment complexity increases
Solution Approach 1:
The combination therapy is segmented into distinct therapeutic components with specific roles: the antibody drug conjugate provides direct cytotoxic activity, the immune checkpoint inhibitor restores T-cell function, and the TIGIT inhibitor enhances anti-tumor immunity. This segmentation allows each agent to be optimized for its specific mechanism while simplifying the overall treatment strategy by assigning clear functional responsibilities to each component
Data Source
AI summary
The present disclosure relates to methods of treating, mitigating, or preventing or delaying the recurrence or metastasis of a cancer in a subject by administering an effective amount of: (a) an antibody-drug conjugate (ADC) comprising (i) an anti-TROP-2 antibody; and/or (ii) a topoisomerase I inhibitor; (b) an anti-PD-(L)1 antibody; and, optionally, (c) an anti-TIGIT antibody.