Recombinant Fusion Protein for Dual PD-1 and TGFβ Targeting
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Solution Overview
Problem
Current cancer treatments targeting single tumor-associated antigens or immune-suppressive pathways have limited therapeutic efficacy, and combination therapies face challenges such as increased pill burden, drug interactions, and adverse effects, necessitating a more effective approach to enhance immune response against cancer cells.
Innovation Solution
A recombinant fusion protein combining a TGFβR2 fragment and an anti-PD-1 antibody or its antigen-binding fragment, which captures TGFβ in the tumor microenvironment and blocks PD-L1-PD-1 interaction, thereby enhancing immune cell function and cancer cell killing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination therapy with multiple pharmaceutical agents is used to target different immune-suppressive pathways, then therapeutic efficacy is improved, but device complexity and ease of operation deteriorate due to increased pill burden and drug interactions
Solution Approach 1:
The patent combines two separate pharmaceutical agents (anti-PD-1 antibody and TGFβR2 fusion protein) into a single fixed-dose combination product. This merging approach maintains the therapeutic benefits of dual-pathway targeting while reducing pill burden and simplifying administration, directly resolving the technical contradiction between improved efficacy and reduced complexity
Solution Approach 2:
The fixed-dose combination product serves multiple functions simultaneously: it targets both PD-1 and TGFβ pathways, provides coordinated dosing, and simplifies the treatment regimen. This multi-functionality allows a single product to deliver the benefits of combination therapy without the complexities of multiple separate administrations
2Reliability
If combination therapy with multiple pharmaceutical agents is used to target different immune-suppressive pathways, then therapeutic efficacy is improved, but object-generated harmful factors worsen due to increased adverse effects
Solution Approach 1:
The fixed-dose combination product optimizes the dosing parameters of both agents by establishing a predetermined ratio and coordinated administration schedule. This parameter optimization ensures that each agent is delivered at its optimal dose, maximizing therapeutic efficacy while minimizing adverse effects through balanced pharmacokinetic profiles
3Device complexity
If single molecule drug having two or more target binding specificities is developed, then device complexity is reduced, but manufacturing precision worsens due to complex protein engineering requirements
Solution Approach 1:
Rather than creating a single complex bispecific antibody, the patent segments the solution into two separate but coordinated molecules: an anti-PD-1 antibody and a TGFβR2 fusion protein. This segmentation simplifies the manufacturing precision requirements for each individual molecule while achieving the therapeutic benefits of dual-targeting through their coordinated action in the fixed-dose combination
Data Source
AI summary
A recombinant fusion protein comprising 1) TGFβR2, or a fragment thereof, capable of binding to TGFβ, and 2) an antibody, or an antigen-binding fragment thereof, that binds to PD-1. Also disclosed are a polynucleotide encoding the recombinant fusion protein, an expression vector containing the polynucleotide, a method for producing the recombinant protein and a method for treating a disease caused by over expression of TGFβ and/or PD-1 using the recombinant protein.