Engineered Proteinaceous Particle for Tumor Penetration
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer immunotherapies, such as checkpoint blockade and CAR-T cells, are ineffective for treating brain cancer, glioblastoma, oesophageal cancer, and ovarian cancer due to challenges in entering tumors and navigating the immunosuppressive tumor microenvironment.
Innovation Solution
Development of engineered proteinaceous particles with a core of granzyme and/or perforin surrounded by a glycoprotein shell comprising thrombospondin-1, which are stable and capable of binding to target cells, releasing cytotoxic enzymes to induce cell death, and can be engineered for specific targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapies (checkpoint blockade, CAR-T cells) are used, then specific subtypes of cancer can be treated, but they are ineffective for brain cancer, glioblastoma, oesophageal cancer, and ovarian cancer due to inability to enter tumors and navigate immunosuppressive microenvironment
Solution Approach 1:
The patent uses engineered proteinaceous particles as intermediaries to deliver cytotoxic payloads (granzyme B and perforin) directly to target cells. These particles overcome the limitations of conventional immunotherapies by serving as stable, engineered carriers that can penetrate into tumors and function in immunosuppressive microenvironments where T cells and NK cells fail.
Solution Approach 2:
The invention modifies the physical and chemical parameters of the therapeutic agent by engineering proteinaceous particles with specific properties: a stable protein core containing cytotoxic enzymes, surrounded by a glycoprotein shell (thrombospondin-1 or variants) that provides stability and targeting capabilities. This engineered structure changes the stability, half-life, and targetability parameters compared to conventional biologics.
2Reliability
If effector cells are used for immunotherapy, then cancer cells can be killed, but effector cells cannot effectively enter tumors in immune-privileged sites like glioblastoma
Solution Approach 1:
The patent extracts the essential cytotoxic function from living effector cells and transfers it into engineered proteinaceous particles. By taking out the cytotoxic payload (granzyme B and perforin) from T cells and NK cells and encapsulating it in stable protein particles, the therapy achieves cellular cytotoxic function without the limitations of cell size, viability, and tissue penetration.
3Reliability
If genetically modified organisms are used to produce engineered proteins, then specific targeting and stability can be achieved, but regulatory requirements and characterization complexity increase
Solution Approach 1:
The patent employs the universally conserved thrombospondin-1 glycoprotein shell, which provides multiple functions: structural stability, protection of the cytotoxic core, and potential targeting capabilities. This universal scaffold can be used across different therapeutic formulations, simplifying development compared to creating entirely new engineered proteins for each application.
Data Source
AI summary
The invention relates to an isolated proteinaceous particle comprising a core of perform and/or granzyme, the core being surrounded by a glycoprotein shell comprising thrombospondin-1 (TSP-1) or a fragment thereof, a variant thereof or an orthologue thereof. The invention further relates to nn engineered proteinaceous particle comprising a core of perform and/or granzyme, the core being surrounded by a glycoprotein shell comprising a thrombospondin protein, or a fragment thereof, a variant thereof or an orthologue thereof, wherein the granzyme and/or the thrombospondin is genetically modified. Further related materials, medical uses and manufacture are also contemplated.