B7-H3 and PD-1 Antibody Combination Therapy
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Solution Overview
Problem
Current therapies fail to effectively activate the immune system against cancers expressing B7-H3, as they are hampered by immune suppressive mechanisms in the tumor microenvironment, including co-inhibitory molecules that attenuate T-cell responses.
Innovation Solution
A combination therapy involving a molecule that specifically binds to human B7-H3 and another that binds to PD-1, administered to enhance immune activation against cancer cells, using specific antibodies or their antigen-binding fragments to compete for binding sites or incorporate specific CDRs and variable domains from known antibodies like BRCA84D and nivolumab.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to treat cancers expressing B7-H3, then the treatment can be administered, but the immune system is not effectively activated against the cancer cells due to immune suppressive mechanisms in the tumor microenvironment
Solution Approach 1:
The therapy is segmented into two distinct molecular components: a first molecule that specifically binds to B7-H3 on tumor cells and a second molecule that specifically binds to PD-1 on T cells. This segmentation allows each molecule to target a specific pathway independently, with the B7-H3 binding molecule providing costimulatory signals and the PD-1 binding molecule blocking inhibitory signals, thereby overcoming immune suppression more effectively than a single therapy
Solution Approach 2:
The patent combines two previously separate therapeutic approaches into a single combination therapy: B7-H3 targeting (which provides costimulation) and PD-1 blocking (which removes inhibition). By merging these two mechanisms that act on different aspects of T cell activation, the therapy achieves synergistic immune activation that overcomes the immune suppressive mechanisms that would block either approach alone
2Reliability
If a single molecule targeting either B7-H3 or PD-1 is used, then the therapy is simpler to administer, but the activation of the immune system against cancer cells is insufficient due to counterbalancing immune suppressive mechanisms
Solution Approach 1:
The combination therapy is segmented into two administrable components that can be given separately or together, allowing flexibility in dosing schedules and routes of administration while maintaining the synergistic effect of targeting both B7-H3 and PD-1 pathways simultaneously
Solution Approach 2:
The first molecule is designed to specifically bind B7-H3 and provide costimulatory signals, while the second molecule is designed to specifically bind PD-1 and block inhibitory signals. Each molecule has a specialized function, but together they create a multi-functional therapy that addresses both the lack of activation and the presence of suppression in the tumor microenvironment
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
This approach enhances the activation of the immune system against cancer cells, overcoming immune suppression and improving treatment outcomes for various human cancers by specifically targeting B7-H3 and PD-1 pathways.
Implementation Method 1
a first molecule that specifically binds to human B7-H3 and a second molecule that that specifically binds to human PD-1
Data Source
AI summary
The present invention is directed to a combination therapy involving the administration of a first molecule that specifically binds to human B7-H3 and a second molecule that specifically binds to human PD-1 to a subject for the treatment of cancer and/or inflammation. The invention also concerns pharmaceutical compositions that comprise a first molecule that specifically binds to human B7-H3 and a second molecule that specifically binds to human PD-1 that are capable of mediating, and more preferably enhancing, the activation of the immune system against cancer cells that are associated with any of a variety of human cancers. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases in recipient subjects.