iNKT Stimulator Structural Modification for Tumor Targeting
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Solution Overview
Problem
Current immunostimulators, such as KRN7000, have limitations in efficiency and therapeutic selectivity for immunotherapy, particularly in cancer treatment, and fail to effectively activate iNKT cells in tumor cells considered 'non-CD1d' without mobilizing canonical antigen-presenting cells.
Innovation Solution
Development of a new family of iNKT stimulators with compounds of specific formulas, including 6-PEGm-NHR-GalCer, which exhibit significantly higher potency than KRN7000, capable of activating iNKT cells on tumor cells expressing low levels of CD1d without requiring canonical antigen-presenting cells, and can be coupled with carriers like antibodies or nanoparticles for targeted delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If KRN7000 is used as an immunostimulator, then iNKT cells can be activated, but the activation potency is insufficient compared to the new compounds
Solution Approach 1:
The patent modifies the chemical structure of KRN7000 by changing parameters at specific positions (6-OH modification with PEG chains, alkyl chains, or branched hydrocarbon groups) to enhance iNKT cell activation potency while maintaining the core GalCer structure
Solution Approach 2:
The new compounds combine the core GalCer structure with additional functional groups (PEG fragments, alkyl chains, carrier molecules) to create composite immunostimulators that exhibit superior activity compared to the simple KRN7000 structure
2Adaptability or versatility
If canonical antigen-presenting cells are used to present antigens, then iNKT cells can be activated, but the system cannot activate iNKT cells on non-CD1d tumor cells
Solution Approach 1:
The new immunostimulators are designed to function universally across different cell types including canonical APCs and non-CD1d tumor cells, eliminating the limitation of requiring specific antigen-presenting cells for activation
3Productivity
If immunostimulators are administered systemically, then broad immune activation occurs, but side effects increase and therapeutic selectivity decreases
Solution Approach 1:
Carrier molecules serve as intermediaries to deliver the immunostimulators specifically to tumor cells or tumor microenvironment, reducing systemic exposure and side effects while maintaining therapeutic efficacy
Solution Approach 2:
The immunostimulators are designed to exert their primary effect locally at the tumor site through targeted delivery, creating high concentration where needed while minimizing exposure to healthy tissues
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
These new iNKT stimulators demonstrate enhanced cytokine release and cytotoxic responses, achieving higher activation potency and selective tumor targeting with reduced side effects, enabling more effective immunotherapy for cancer and other diseases.
Implementation Method 1
these cells rapidly release copious quantities of cytokines able to initiate or amplify an immune response
Data Source
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AI summary
The present invention relates to a new family of iNKT stimulators, referred to as 6"-O-PEGm-NHR-GalCer, which are potent analogues of KRN7000. These iNKT stimulators can advantageously be used in therapy, in particular for the prevention and/or treatment of many diseases requiring a stimulation of an immune response, such as cancer, viral, bacterial or parasitic diseases, autoimmune diseases or inflammatory diseases. The iNKT cell stimulator of the invention may be coupled to a biological carrier, such as a therapeutic and/or targeting agent, or be vectorized, for example in nanoparticles, to be specifically delivered to target cells.