HPV E7-Fibronectin EDA Conjugate for Dendritic Cell Maturation
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Solution Overview
Problem
Current immunogenic compositions for HPV and cervical cancer treatment often require high doses and may cause unwanted cell transformation, necessitating the development of compositions that generate an immune response without transforming cells and can act synergistically to reduce protein doses.
Innovation Solution
A conjugate comprising the fibronectin EDA region covalently coupled with HPV E7-derived antigenic peptides, combined with TLR ligands and chemotherapeutic agents, to induce cytotoxic responses and enhance antitumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of immunogenic compositions are used, then immune response is enhanced, but unwanted cell transformation occurs
Solution Approach 1:
The patent uses dendritic cells as intermediary carriers that present HPV E7 peptides to T cells, enabling immune response activation without direct exposure to high doses of viral proteins that cause transformation. The dendritic cells process and present antigenic peptides through MHC molecules, serving as a safe mediator between the virus and the immune system.
Solution Approach 2:
The patent segments the HPV E7 protein into specific antigenic peptides (epitopes) that are presented to T cells. Instead of using the complete viral protein which causes transformation, only specific peptide segments are used, reducing the harmful effects while maintaining immune recognition capability.
2Ease of operation
If single immunogenic compositions are used, then treatment simplicity is maintained, but sufficient immune response is not generated
Solution Approach 1:
The patent combines multiple immunogenic compositions in a single treatment regimen: dendritic cells pulsed with HPV E7 peptides, interferon gamma, and IL-2. This combination synergistically enhances immune response while maintaining treatment simplicity through a unified protocol that integrates multiple components working together.
Solution Approach 2:
The patent creates a composite immunogenic composition that integrates dendritic cells, peptide antigens, and cytokines into a single therapeutic formulation. This composite approach provides comprehensive immune stimulation while simplifying administration compared to separate treatments.
3Reliability
If high doses of protein are administered, then antitumor activity is increased, but cost and toxicity increase
Solution Approach 1:
Dendritic cells serve as intermediaries that process and present peptide antigens, eliminating the need for high doses of viral proteins. The cells internally process the peptides and present them on MHC molecules, reducing protein quantity requirements while maintaining effective T cell activation and antitumor activity.
Solution Approach 2:
The patent uses partial action by employing only specific antigenic peptides rather than complete viral proteins. This partial approach provides sufficient immune stimulation with much lower protein doses, avoiding excessive toxicity and cost while achieving the desired antitumor effect.
Data Source
Figure 1A~1C
Figure 2
Figure 3A~3B
AI summary
The invention relates to immunogenic conjugates comprising an immunogenic region of human papilloma virus E7 protein and the fibronectin EDA region, as well to compositions comprising said conjugates and to dendritic cells obtained by stimulation with said conjugates and compositions. Moreover, the invention relates to methods for the treatment of diseases caused by the human papilloma virus (HPV) using said conjugates, compositions and dendritic cells.