Fc-Effector-Null Anti-CD137 Antibodies for Anti-PD-1 Efficacy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current agonistic antibodies targeting human CD137 have not demonstrated sufficient responses as a monotherapy or combination therapy in human patients, and existing combinations with anti-PD-1 antibodies are limited by adverse events and sub-optimal efficacy, necessitating the development of improved antibodies with enhanced pharmacological attributes.
Innovation Solution
Development of engineered human Fcγ-receptor-mediated effector null antibodies that agonize the human CD137 receptor, promoting T cell activation, enhancing NF-kappa B activity, and inhibiting tumor growth, while being designed to combine effectively with anti-PD-1 antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If agonistic antibodies targeting human CD137 are used as monotherapy or combination therapy, then T cell activation and anti-tumor immune response are enhanced, but sufficient therapeutic response is not achieved in human patients
Solution Approach 1:
The patent combines agonistic anti-CD137 antibodies with anti-PD-1 antibodies to create a combination therapy that synergistically enhances T cell activation and anti-tumor immune response, overcoming the limitations of monotherapy approaches
Solution Approach 2:
The patent modifies antibody parameters including isotype selection (IgG1, IgG2, IgG4), Fc region engineering, and dosing regimens to optimize the balance between activating anti-tumor immunity and managing toxicity, thereby improving therapeutic response
2Productivity
If agonistic antibodies targeting human CD137 are combined with anti-PD-1 antibodies, then anti-tumor immune response is enhanced, but adverse events occur
Solution Approach 1:
The patent engineers antibodies with modified Fc regions and selects specific isotypes to modulate effector function and cytokine release, thereby enhancing anti-tumor efficacy while reducing immune-related adverse events through controlled immunomodulation
Solution Approach 2:
The patent uses Fc region engineering as an intermediary mechanism to fine-tune the interaction between antibodies and immune cells, allowing optimization of therapeutic effect while minimizing harmful immune activation
3Reliability
If existing combinations with anti-PD-1 antibodies are used, then some therapeutic effect is achieved, but sub-optimal efficacy limits clinical success
Solution Approach 1:
The patent optimizes multiple parameters including antibody affinity, isotype, Fc engineering, and dosing schedules to maximize the therapeutic index, transforming existing sub-optimal combinations into highly effective treatments with improved clinical outcomes
Data Source
AI summary
The present invention relates to antibodies that bind to human CD137 and display agonist activity, and may be useful for treating solid and hematological tumors alone and in combination with anti-human PD-1 antibodies, chemotherapy, and ionizing radiation.