Engineered Platelets with Chimeric Receptors for Targeted Delivery
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Solution Overview
Problem
Current cell therapies, such as CAR-T cells, face safety concerns and limitations in generating universal therapeutic products due to oncogenic transformation and patient matching issues, restricting their use in treating cancer, autoimmune conditions, and infections.
Innovation Solution
Development of engineered platelets with a chimeric platelet receptor (CPR) that includes an intracellular domain with an immunoreceptor tyrosine-based activation motif (ITAM) and a heterologous targeting domain, allowing for targeted therapeutic delivery systems that do not require patient matching and have reduced immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T cells are used for cancer therapy, then therapeutic effectiveness is improved, but safety concerns arise due to oncogenic transformation and patient matching requirements
Solution Approach 1:
The invention segments the therapeutic approach by using platelets as separate delivery vehicles that can be engineered with specific receptors and therapeutic cargo, rather than modifying the patient's own T cells. This allows the therapeutic function to be separated from the safety risks of cellular transformation.
Solution Approach 2:
The patent employs platelets as disposable, short-lived delivery vehicles that naturally circulate for only about 10 days before being cleared by macrophages. This eliminates the long-term safety concerns associated with engineered T cells that could potentially transform into cancer, while still providing effective therapeutic delivery during their functional lifespan.
2Adaptability or versatility
If CAR-T cells are engineered for targeted therapy, then treatment specificity is improved, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The invention creates a universal platelet-based delivery system that can be engineered with different chimeric platelet receptors (CPRs) targeting various antigens. The same basic platelet platform can be adapted for different cancers and diseases by simply changing the receptor and cargo, eliminating the need for complex, disease-specific cell engineering processes.
Solution Approach 2:
The patent changes key parameters of platelets through genetic engineering - introducing chimeric platelet receptors with specific extracellular binding domains and intracellular stimulation domains, and loading therapeutic cargo. These parameter changes allow targeted delivery without requiring complex manufacturing processes.
3Adaptability or versatility
If platelets are engineered with chimeric receptors for targeted delivery, then therapeutic targeting is improved, but thrombogenic potential may increase
Solution Approach 1:
The invention extracts the thrombogenic functions from the platelet while retaining the delivery capability. By using enucleated platelets as passive delivery vehicles that are naturally cleared by macrophages, the system eliminates the risk of thrombosis formation while maintaining targeted therapeutic delivery through engineered chimeric platelet receptors.
Data Source
AI summary
The present invention provides engineered platelets with chimeric platelet receptors (CPR) with a desired target specificity. Additionally, the engineered platelets may comprise cargo which may be released upon activation of the platelet. Additionally, the platelets may be generated in vitro from megakaryocytes engineered to generate non-thrombogenic platelets.