Extracellular TCTP-Binding Molecule for Tumor Immune Suppression
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Solution Overview
Problem
The tumor immune microenvironment suppresses immune responses against tumor cells, limiting the efficacy of cancer immunotherapy, and the function of TCTP outside cells has not been fully understood.
Innovation Solution
A novel binding molecule that specifically binds to extracellular TCTP with a dissociation constant of 1×10−7 M or less, inhibiting suppressive immune cells and activating anti-cancer immune cells by targeting TCTP or its cleaved forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TCTP is released from tumor cells and acts as an immunoregulatory factor in the tumor immune microenvironment, then immune suppression is enhanced, but the function of TCTP outside cells remains unclear
Solution Approach 1:
The patent uses an anti-TCTP antibody as an intermediary molecule to bind to extracellular TCTP and block its immunosuppressive function. The antibody serves as a mediator that interferes with the interaction between TCTP and its receptors on immune cells, thereby reversing immune suppression without requiring complete understanding of all TCTP extracellular functions.
2Quantity of substance
If nucleic acid molecules (antisense oligonucleotides, SiRNA, shRNA) are used to suppress TCTP expression in cells, then intracellular TCTP levels are reduced, but extracellular TCTP function remains unaddressed
Solution Approach 1:
The patent extracts and targets the extracellular form of TCTP specifically, separating it from intracellular TCTP. By using an antibody that binds to extracellular TCTP, the invention addresses the extracellular function independently of intracellular expression levels, thereby providing comprehensive coverage that nucleic acid molecules alone cannot achieve.
Solution Approach 2:
The patent changes the approach from modifying gene expression (intracellular parameter) to directly targeting the protein product in the extracellular space. This parameter change allows simultaneous addressing of both intracellular and extracellular TCTP functions by combining nucleic acid molecules with antibody therapy.
3Object-affected harmful factors
If the tumor immune microenvironment suppresses immune responses, then cancer immunotherapy efficacy is limited, but the mechanism involves multiple cell types and interactions
Solution Approach 1:
The patent extracts TCTP as a specific target from the complex tumor immune microenvironment. By identifying and targeting TCTP, which is released by tumor cells and acts on multiple immune cell types, the invention simplifies the complex TIME interactions into a single actionable target that can be blocked by anti-TCTP antibodies.
Solution Approach 2:
The patent exploits the universal role of TCTP in mediating immune suppression across multiple immune cell types (T cells, NK cells, macrophages). A single anti-TCTP antibody can block TCTP's interaction with various receptors on different immune cells, providing a universal solution to the multifaceted problem of TIME-mediated immune suppression.
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 binding molecule suppresses the function of suppressive immune cells and activates anti-cancer immune cells, enhancing the immune response against tumors, thereby improving cancer treatment outcomes.
Implementation Method 1
a dissociation constant (Kd) of about 1×10−7 M or less or 5×10−8 M or less in a case of being measured by surface plasmon resonance
Data Source
AI summary
A novel binding molecule or a fragment thereof and uses thereof are disclosed. The novel binding molecule or a fragment thereof specifically bind to an extracellular translationally controlled tumor protein (TCTP). The binding molecule and the fragment thereof can be used to diagnose, treat, or prevent cancer. The binding molecule and the fragment thereof can be used to alleviate or prevent immune suppression in a tumor immune microenvironment. The binding molecule and the fragment thereof can be used to diagnose, treat, or prevent cancer in a patient who has no response, has a limited response, or is likely to have such a response to treatment using a cancer immunotherapeutic agent.