Anucleate Cell Vesicles for Robust Mutated Ras T Cell Responses
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Solution Overview
Problem
Current therapies for K-Ras mutant cancers, such as pancreatic, colon, and lung cancers, have not been successful, and existing immunotherapy methods face challenges in inducing robust T cell responses against mutated Ras antigens.
Innovation Solution
Administering anucleate cell-derived vesicles, such as red blood cell-derived vesicles, intracellularly loaded with mutated Ras antigens and optionally with adjuvants, to stimulate an immune response by passing cells through a constriction to perturb and deliver the antigens or their encoding nucleic acids into the vesicles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy methods are used to treat K-Ras mutant cancers, then treatment approaches have been attempted for three decades, but robust T cell responses against mutated Ras antigens have not been induced
Solution Approach 1:
The patent uses anucleate cell-derived vesicles as intermediary carriers to deliver mutated Ras antigens to the immune system. These vesicles act as mediators that facilitate antigen presentation and T cell activation, resolving the contradiction by providing an effective delivery mechanism that conventional methods failed to achieve.
Solution Approach 2:
The patent employs synthetic vesicles that replicate the functional characteristics of natural cell membranes and vesicles. These artificial vesicles carry and present antigens in a manner that mimics biological systems, enabling robust T cell responses without using actual tumor cells or nucleated cells.
2Quantity of substance
If nucleated cells are used to deliver mutated Ras antigens, then antigen delivery can be achieved, but the complexity of handling and manufacturing increases
Solution Approach 1:
The patent extracts the nucleus from the cell structure, using anucleate cells as the basis for vesicle generation. This removal of the nuclear component simplifies the cells for manufacturing purposes while maintaining their ability to form functional vesicles that can deliver antigens effectively.
Solution Approach 2:
The patent modifies the physical and chemical parameters of the vesicles, including their size, surface properties, and cargo capacity, to optimize antigen delivery. By controlling these parameters during vesicle formation and loading, the patent achieves efficient antigen delivery with reduced manufacturing complexity.
Data Source
AI summary
The present application provides anucleate cells comprising a mutated Ras antigen (such as a mutated K-Ras antigen), methods of manufacturing such anucleate cells comprising the mutated Ras antigen, and methods of using such modified anucleate cells for stimulating an immune response, treating, and/or vaccinating an individual with a cancer associated with Ras mutation.