Chimeric Proteins Tumor Targeting via Oncolytic Vectors
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Solution Overview
Problem
Current cancer immunotherapy approaches using chimeric proteins often exhibit toxicity systemically due to their broad activity, rather than being targeted specifically to tumor tissues, limiting their efficacy and safety.
Innovation Solution
Development of nucleic acids encoding chimeric proteins with specific structures, including signaling and targeting domains, linked by functional linkers, to be expressed locally within the tumor microenvironment using gene therapy vectors like oncolytic viruses, ensuring targeted immune responses and minimizing systemic toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chimeric proteins are used for cancer immunotherapy, then anti-tumor efficacy is improved, but systemic toxicity increases
Solution Approach 1:
The patent applies local quality by engineering chimeric proteins with tumor-specific targeting domains that concentrate the immunotherapeutic activity exclusively at the tumor site. The targeting domain directs the chimeric protein to bind specifically to tumor cells, while the immunostimulatory domain activates immune cells locally, thereby maintaining anti-tumor efficacy while minimizing systemic toxicity through spatial localization of the therapeutic effect.
Solution Approach 2:
The patent uses an oncolytic virus as an intermediary delivery system that selectively transports the chimeric protein genes to tumor cells. The oncolytic virus acts as a mediator by preferentially infecting and replicating in tumor cells, thereby releasing the chimeric protein locally at the tumor site and avoiding systemic distribution, thus resolving the contradiction between efficacy and toxicity.
2Object-affected harmful factors
If chimeric proteins are vectorized to tumor microenvironment using gene therapy vectors, then safety is improved, but treatment complexity increases
Solution Approach 1:
The patent employs oncolytic viruses that perform multiple functions simultaneously: they selectively infect tumor cells, replicate within them to cause lysis, and serve as delivery vectors for the chimeric protein genes. This multi-functionality consolidates several therapeutic mechanisms into a single agent, improving safety through targeted delivery while managing complexity by using a versatile platform technology.
3Reliability
If additional functional domains are added to chimeric proteins, then immunostimulatory properties are enhanced, but protein complexity increases
Solution Approach 1:
The patent merges multiple functional domains within a single chimeric protein structure, including targeting domains for tumor specificity and multiple immunostimulatory domains that engage different immune checkpoints or co-stimulatory receptors. This consolidation of multiple functions into one integrated molecule enhances immunostimulatory properties while managing complexity through rational protein design and standardized modular domains.
Data Source
AI summary
Chimeric proteins for cancer immunotherapy can combine different activities by displaying both agonistic and antagonistic properties on a single molecule. However, those usually exhibit toxicities related to their potency being exerted in the entire organism and not only in tissues relevant for cancer treatment. This may be solved by using appropriate vectorization of the chimeric proteins to the tumour microenvironment, where immune cells interact with tumour cells expressing immunomodulatory molecules. The present invention relates to a nucleic acid encoding a chimeric protein or a chimeric protein having a general structure of: N terminus-(a)-(b)-(c)-C terminus, wherein: (a) is a signaling and/or targeting domain. (b) is a linker (b) is a functional linker and (c) is a signaling and/or targeting domain or N terminus-(c)-(b)-(a)-C terminus, wherein: (c) is a signaling and/or targeting domain. (b) is a linker (b) is a functional linker and (a) is a signaling and/or targeting domain.