Anti-CD73 Antibody–IL-2 Fusion Protein for T-Cell Activation
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Solution Overview
Problem
Existing cancer treatments fail to effectively activate immune cells and control the tumor microenvironment, leading to immunosuppression and cancer cell evasion.
Innovation Solution
A fusion protein dimer comprising an anti-CD73 antibody or its antigen-binding fragment and IL-2 is developed to inhibit adenosine production, blocking the A2AR and A2BR signaling pathways, thereby activating immune cells and controlling the tumor microenvironment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments are used, then treatment is provided, but immune cells are not effectively activated and tumor microenvironment control is achieved
Solution Approach 1:
The patent combines anti-CD73 antibody and IL-2 into a single fusion protein molecule, creating a dual-functional agent that simultaneously blocks adenosine production and activates immune cells. This merging resolves the contradiction by delivering two therapeutic actions through one molecule, overcoming both immunosuppression and ineffective immune activation
Solution Approach 2:
The fusion protein represents a composite biological material combining two distinct functional components (anti-CD73 antibody and IL-2) into one integrated molecule. This composite structure enables simultaneous inhibition of the adenosine pathway and direct immune cell stimulation, addressing the limitations of conventional single-agent treatments
2Object-generated harmful factors
If adenosine signaling pathway is active, then immune suppressor cells are activated, but cytotoxic T cell and NK cell activity is inhibited
Solution Approach 1:
The anti-CD73 antibody component of the fusion protein preemptively blocks CD73 enzyme activity, preventing adenosine production before it can activate immune suppressor cells. This preliminary action stops the harmful signaling cascade at its source, protecting cytotoxic T cells and NK cells from suppression
Solution Approach 2:
The fusion protein converts the harmful adenosine signaling pathway into a benefit by blocking CD73, thereby preventing immunosuppression. Simultaneously, the IL-2 component harnesses immune cell activity for anti-tumor purposes, transforming potential harm into therapeutic benefit
3Reliability
If IL-2 is used alone, then immune cell activity is enhanced, but tumor microenvironment control is insufficient
Solution Approach 1:
By merging anti-CD73 antibody and IL-2 into one fusion protein, the invention ensures that immune cell activation (via IL-2) occurs simultaneously with blockade of the immunosuppressive adenosine pathway (via anti-CD73). This resolves the contradiction by making the two actions inseparable, ensuring tumor microenvironment control accompanies immune 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 fusion protein activates CD8+ and CD4+ T cells while inhibiting immunosuppressive cells, providing a therapeutic approach for cancer treatment by enhancing immune cell activity and inhibiting tumor growth.
Implementation Method 1
an antibody or a fragment thereof that specifically binds to CD73
Implementation Method 2
blocking the A2AR and A2BR signaling pathways
Data Source
AI summary
A fusion protein in which an anti-CD73 antibody or an antigen-binding fragment thereof and IL-2 are linked to each other, and the use thereof are disclosed. The fusion protein or dimer thereof contains an anti-CD73 antibody or an antigen-binding fragment thereof and IL-2, and is able to inhibit adenosine production by binding to CD73 of cancer cells, thereby blocking the A2AR and A2BR signaling pathways, thus controlling the tumor microenvironment. Furthermore, the fusion protein or dimer thereof is able to activate immune cells (CD8+ T cells and CD4+ T cells) along with less activation of immunosuppressive cells such as regulatory T cells (Tregs). In addition, IL-2 or a variant thereof in the fusion protein is able to activate immune cells. Therefore, the fusion protein and dimer thereof may be useful for preventing or treating cancer.


