dPSA-Binding Antibody Targeting De-N-Acetylated PolySia for Cancer Therapy
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Solution Overview
Problem
Current anti-cancer immunotherapies face challenges in identifying stable tumor antigens that are highly expressed on cancer cells but not on normal cells, leading to potential side effects due to cross-reactivity, and there is a need for agents that can target the de-N-acetylated form of polySia (dPSA) specifically found on cancer cells.
Innovation Solution
Development of dPSA-binding agents comprising immunoglobulin heavy and light chain polypeptides that selectively bind to dPSA on cancer cells, which can be used for targeted therapy, diagnosis, or delivery of therapeutic payloads.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapies use stable tumor antigens highly expressed on cancer cells, then therapeutic efficacy is improved, but cross-reactivity with normal cells causes harmful side effects
Solution Approach 1:
The patent applies local quality by targeting a specific post-translational modification (de-N-acetylation of polySia) that is locally present on cancer cell surfaces but absent on normal cells. This localized chemical distinction allows the antibody to differentiate between cancerous and normal tissues, achieving high therapeutic efficacy while minimizing cross-reactivity and side effects.
Solution Approach 2:
The invention exploits a parameter change in the glycosylation state of cell surface proteins - specifically the de-N-acetylation of polySia residues. This chemical modification parameter distinguishes cancer cells from normal cells, enabling the antibody to selectively bind to cancer cells expressing dPSA while avoiding normal cells, thus resolving the contradiction between efficacy and safety.
2Measurement precision
If tumor antigens are targeted for immunotherapy, then cancer cells can be identified and treated, but cross-reactivity with non-cancerous cells reduces treatment specificity
Solution Approach 1:
The antibody targets a locally unique feature - de-N-acetylated polySia residues - that are present on cancer cell surfaces but absent from normal cells. This localized chemical distinction provides high measurement precision for cancer cell identification while eliminating cross-reactivity with normal tissues.
Solution Approach 2:
Instead of targeting proteins that are overexpressed on both cancer and normal cells (leading to cross-reactivity), the patent inverts the approach by targeting a modified form (de-N-acetylated polySia) that is uniquely present on cancer cells. This inverted strategy achieves high specificity by binding to what is unique to cancer cells rather than what is merely overexpressed.
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 dPSA-binding agents effectively target and kill cancer cells, reducing side effects by minimizing cross-reactivity with normal cells, and demonstrate ADCC activity and tumor growth inhibition in xenograft models.
Implementation Method 1
dPSA-binding agents comprising immunoglobulin heavy and light chain polypeptides that selectively bind to dPSA on cancer cells
Implementation Method 2
demonstrate ADCC activity and tumor growth inhibition in xenograft models
Data Source
AI summary
A dPSA-binding agent and immunoglobulin heavy chain and light chain polypeptides of the binding agent, as well as methods of using the dPSA-binding agent to treat cancer and kill cancer cells.