TGF-β1 Antibodies Activate Latent Cytokine via LAP Binding
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Solution Overview
Problem
There is a need for antibodies that can bind to and activate TGF-β1 to increase immunosuppressive activity, particularly for treating autoimmune and allo-immune diseases, as well as for enhancing tumor-suppressive activities in cancer.
Innovation Solution
Development of antibodies or antigen binding fragments that specifically bind to latent TGF-β1, thereby activating the mature TGF-β1 cytokine by releasing it from the inhibition exerted by the latency-associated peptide (LAP) region.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies bind to latent TGF-β1 to activate it, then immunosuppressive activity is enhanced, but the complexity of the therapeutic system increases
Solution Approach 1:
The patent extracts and isolates specific antibody molecules that target latent TGF-β1, separating the activation function from the complex cellular environment. By identifying and purifying specific antibody clones (such as those binding to the LAP region), the invention simplifies the therapeutic approach while maintaining enhanced immunosuppressive activity.
Solution Approach 2:
The antibodies serve as intermediary molecules that mediate between the latent TGF-β1 storage form and its active signaling state. These antibody intermediaries bind to latent TGF-β1 and facilitate its conversion to active form, thereby controlling immunosuppressive activity without requiring direct manipulation of the complex TGF-β signaling pathway.
2Reliability
If latent TGF-β1 is activated by antibody binding, then tumor-suppressive effects are enhanced, but the specificity of action may be reduced
Solution Approach 1:
The patent applies local quality by designing antibodies with specific binding sites targeted at particular regions of latent TGF-β1, such as the LAP domain or conserved epitopes. This localized binding ensures that activation occurs only at the intended target site, enhancing tumor-suppressive effects while minimizing off-target effects and maintaining action specificity.
3Reliability
If TGF-β1 activation is increased for autoimmune disease treatment, then immune response is suppressed, but potential harmful effects on normal immunity increase
Solution Approach 1:
The patent employs partial action by developing antibodies that selectively activate TGF-β1 under specific conditions rather than causing complete or excessive activation. The antibodies are designed to trigger TGF-β1 signaling only when and where needed, providing sufficient immune suppression for autoimmune disease treatment while avoiding harmful effects on normal immune function through controlled, partial activation.
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
The antibodies effectively activate TGF-β1, enhancing its immunosuppressive and tumor-suppressive effects, which can be therapeutically beneficial in managing autoimmune diseases and cancer.
Implementation Method 1
antibodies capable of activating TGF-β1, i.e., antibodies that can bind to latent TGF-β1 and release the mature TGF-β1 cytokine from the inhibition exerted by the LAP region of the full-length TGF-β1 protein
Data Source
AI summary
Antibodies capable of activating TGF-β1, or antigen binding fragments thereof, in particular antibodies that can bind to latent TGF-β1 and release the mature TGF-β1 cytokine. Additionally, pharmaceutical compositions including the antibodies, or antigen binding fragments thereof. Also, methods in which the antibodies, or antigen binding fragments thereof, or the pharmaceutical compositions are administered to a subject in need thereof.