Fusion Polypeptide Vaccines for Tumor Angiogenesis Self-Antigens
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Solution Overview
Problem
Current anti-angiogenic cancer drugs show limited efficacy and severe side-effects due to the induction of drug resistance and the challenge of inducing a suitable immune response against tumor-specific self-antigens, while existing fusion proteins face issues with overt antigenicity suppressing the humoral immune response against the self-antigen.
Innovation Solution
Designing a fusion polypeptide with a truncated, hydrophilic, bulky amino acid residue-containing foreign antigen to redirect the immune response, reducing the antibody response to the foreign antigen and enhancing the response to the self-antigen, thereby eliciting a clinically relevant immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If foreign-self protein fusions are used to induce immune response against self-antigens, then immune response against self-antigens is enhanced, but humoral immune response against foreign antigen increases which suppresses the desired response
Solution Approach 1:
The patent extracts only the essential immunogenic portion of the foreign antigen by using truncated versions (e.g., truncated flagellin, truncated thioredoxin) that retain T-cell epitopes but lack the full immunogenicity of the native foreign protein. This extraction allows the foreign component to serve as a carrier without dominating the immune response
Solution Approach 2:
The patent modifies the parameters of the foreign antigen by truncating it to reduce its immunogenicity while preserving its ability to present self-antigen epitopes. The truncated foreign protein maintains structural features necessary for antigen presentation but has reduced capacity to elicit strong anti-foreign antibody responses
2Productivity
If current anti-angiogenic drugs are used to inhibit tumor growth, then tumor-derived growth is inhibited, but drug resistance is induced and therapeutic effect is limited
Solution Approach 1:
The patent introduces a new intermediary mechanism - vaccination with foreign-self fusion proteins - that activates the patient's own immune system to target tumor antigens. This immune-mediated approach complements or replaces direct pharmacological inhibition, providing an alternative pathway to achieve tumor growth inhibition without inducing drug resistance
Solution Approach 2:
The patent enables the patient's immune system to serve itself by generating autoantibodies against self-antigens presented on the fusion protein. The immune system naturally recognizes and responds to the self-antigen portion without requiring foreign antibody administration, creating a self-sustaining therapeutic effect
3Reliability
If human antibodies against self antigens are produced to treat cancer, then therapeutic specificity is improved, but immunological tolerance mechanisms prevent antibody generation
Solution Approach 1:
The patent uses a foreign protein carrier as an intermediary to bridge the gap between self-antigens and the immune system. The foreign carrier acts as a delivery vehicle that overcomes central and peripheral tolerance mechanisms, allowing B-cells to be activated against self-antigens without triggering autoimmune rejection or tolerance
Solution Approach 2:
The patent performs preliminary action by pre-conjugating self-antigens to foreign protein carriers before administration. This pre-prepared fusion protein structure ensures that when the vaccine is administered, the immune system is immediately presented with self-antigens in a format that bypasses tolerance checkpoints, accelerating the generation of therapeutic antibodies
Data Source
AI summary
The invention is in the field of medicine. More specifically, it is in the field of diagnosing tumor angiogenesis status and in the field of medical treatment of a subject who is suffering, suspected to suffer, or might suffer from a tumor in the future. In particular, the invention relates to a fusion polypeptide comprising a foreign antigen and a self antigen, wherein said foreign antigen consists of a polypeptide comprising an amino acid sequence of at least 12-15 amino acid residues, 12-24% of which residues are hydrophilic, bulky amino acid residues selected from the group consisting of histidine, glutamate, arginine, glutamine, aspartic acid and/or lysine.