GRP94 Mini-Chaperone Proteins for Immune Response
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Solution Overview
Problem
Current understanding of GRP94's role in immunomodulation and its potential therapeutic applications is limited, particularly in cancer treatment and embryogenesis, with unclear mechanisms of peptide binding and antigen presentation.
Innovation Solution
Development of nucleic acids encoding truncated GRP94 mini-chaperone proteins and their complexes with biologically relevant peptides, administered to stimulate immune responses in cancer and viral infections, along with GRP94-deficient mouse models for therapeutic agent screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If GRP94 is used to enhance immune response against tumors, then cytotoxic T cell response is improved, but understanding of its role in embryogenesis and basic cellular functions may be compromised
Solution Approach 1:
The patent creates GRP94-deficient mouse models by segmenting the study into specific genetic modifications (knockout models) to isolate and study GRP94's specific functions in immune response versus embryogenesis separately, allowing targeted investigation without confounding variables
Solution Approach 2:
The patent uses transgenic mouse models as intermediaries to study GRP94 function - the mice serve as a model system that allows researchers to investigate GRP94's role in immune response and embryogenesis without directly manipulating human systems, providing a controlled experimental platform
2Ease of manufacture
If truncated GRP94 mini-chaperone proteins are developed for therapeutic use, then ease of manufacture is improved, but functional completeness may be reduced
Solution Approach 1:
The patent extracts and isolates the essential functional domains of GRP94 by creating truncated mini-chaperone proteins that contain only the critical peptide-binding and antigen-presenting regions, removing non-essential portions to simplify production while retaining therapeutic function
Solution Approach 2:
The patent applies local quality by concentrating the functional activity in specific regions of the GRP94 protein - the truncated versions retain the essential N-terminal domain responsible for peptide binding and immune stimulation, while eliminating C-terminal regions that are less critical for the primary therapeutic mechanism
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enhances immune response against tumors and viral infections by mounting cytotoxic T cell responses and provides a tool for screening therapeutic agents targeting GRP94 activity, shedding light on its essential functions in embryonic development and immune modulation.
Implementation Method 1
GRP94 resides in the endoplasmic reticulum and is a molecular chaperone or stress protein which is a member of the heat shock protein (HSP) 90 family. HSP 90 proteins are ligand regulated and participate in the conformational maturation of protein substrates
Implementation Method 2
GRP94 within tumors binds peptides, is released from dying cells and then is taken up by macrophages and/or dendritic cells, where the peptide dissociates from GRP94 and is transferred onto class I histocompatibility proteins
Implementation Method 3
such mutated proteins should be recognized as foreign and elicit vigorous immune response by the T cell arm of the immune system. this so-called 'peptide re-presentation' pathway leads to enhanced killer cell activity against the tumors
Data Source
AI summary
Mini chaperones and methods of use thereof for the treatment of cancer and other disorders are provided. Also provided are tools to facilitate screening therapeutic agents which have selective binding affinity for GRP94.