HER2-Targeting Immunoconjugate with PEG Linker
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Solution Overview
Problem
Current methods for delivering neoantigens to overcome immune ignorance in tumor growth are limited in reaching inaccessible tumors and expanding treatment options for cancer patients.
Innovation Solution
Development of an immunoconjugate comprising an antibody construct that binds to HER2 linked with adjuvants via a polyethylene glycol (PEG) linker, enhancing the activation of antigen-presenting cells and immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to deliver neoantigens to tumor cells, then immune response activation is limited, but the ability to reach inaccessible tumors and expand treatment options is insufficient
Solution Approach 1:
The patent combines an anti-HER2 antibody with adjuvant molecules into a single immunoconjugate molecule. This merging allows the delivery system to simultaneously target HER2-positive tumors while providing in-situ adjuvant delivery to activate antigen-presenting cells directly at the tumor site, thereby improving both immune response activation and applicability to inaccessible tumors through targeted delivery
Solution Approach 2:
The immunoconjugate acts as an intermediary that bridges the antibody's tumor-targeting capability with the adjuvant's immune-stimulating function. The conjugate delivers the adjuvant specifically to the tumor microenvironment, enabling immune activation where it is most needed while maintaining the ability to reach various tumor types through the antibody's targeting mechanism
2Reliability
If intratumoral injections of antibody-tumor immune complexes are used, then robust anti-tumor immunity is achieved, but treatment options for cancer patients with inaccessible tumors are limited
Solution Approach 1:
By merging the antibody and adjuvant into a single conjugate, the patent eliminates the need for complex intratumoral injection procedures. The conjugate can be administered through standard injection methods and will self-target to the tumor, achieving robust immunity without requiring surgical or invasive delivery techniques
Solution Approach 2:
The immunoconjugate is designed to self-target to HER2-positive tumors through the antibody component, eliminating the need for manual intratumoral injection. The conjugate autonomously navigates to the tumor site and releases the adjuvant in-situ, making treatment accessible to patients with tumors in difficult-to-reach locations
Data Source
AI summary
The invention provides an immunoconjugate of formula:or pharmaceutically acceptable salt thereof, wherein subscript r is an integer from 1 to 10, subscript n is an integer from about 2 to about 25, and “Ab” is an antibody construct that has an antigen binding domain that binds HER2. The invention further provides compositions comprising and methods of treating cancer with the immunoconjugate.