Modified Peptides Eliminating LPS Binding for Cancer Therapy
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Solution Overview
Problem
Current cancer therapies, including those using Toll-like receptor agonists and peptides derived from the Limulus anti-LPS factor protein, face challenges such as toxicity, immunodepression, and unwanted immune responses, particularly in patients with concomitant infections or thromboembolic diseases, due to their binding capabilities to LPS and heparin, which can exacerbate conditions and reduce therapeutic efficacy.
Innovation Solution
Development of peptides derived from the 32-51 region of the Limulus anti-LPS factor protein with specific amino acid substitutions that eliminate LPS- and heparin-binding capacity, enhancing anti-tumoral and immunomodulatory effects while promoting a Th1 immune response, thereby reducing toxicity and improving treatment outcomes for cancer and metastasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides derived from Limulus anti-LPS factor protein are used to treat cancer, then anti-tumoral and immunomodulatory effects are enhanced, but binding to LPS and heparin causes toxicity and unwanted immune responses
Solution Approach 1:
The patent extracts and eliminates the harmful binding capability of the peptide to LPS and heparin through specific amino acid substitutions, while preserving the beneficial immunomodulatory and anti-tumoral functions. This is achieved by modifying the peptide sequence to remove the LPS-binding domain while retaining the Th1 immune response activation capability
Solution Approach 2:
The patent changes the chemical parameters of the peptide by introducing specific amino acid substitutions that alter its binding properties. These parameter changes eliminate LPS and heparin binding affinity while maintaining or enhancing the peptide's ability to induce Th1 immune responses and exhibit anti-tumoral activity
2Reliability
If peptides with LPS-binding capacity are used, then immunomodulatory effects are achieved, but binding to heparin exacerbates thromboembolic conditions
Solution Approach 1:
The patent removes the heparin-binding capability from the peptide through specific amino acid substitutions, thereby eliminating the harmful effect of exacerbating thromboembolic conditions while preserving the desired immunomodulatory functions
Solution Approach 2:
The patent modifies the peptide's chemical parameters by substituting specific amino acids that are responsible for heparin binding, thereby changing the peptide's affinity profile to exclude heparin while maintaining immunomodulatory activity
3Adaptability or versatility
If current cancer therapies are used, then treatment options are available, but toxicity and immunodepression occur
Solution Approach 1:
The patent employs amino acid substitutions to change the peptide's properties, achieving a therapeutic profile that maintains anti-tumoral efficacy while reducing toxicity and immunodepression side effects
Solution Approach 2:
The patent creates a modified peptide composite that combines the beneficial immunomodulatory properties of the original peptide with reduced harmful interactions, achieving a more favorable therapeutic index
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
The peptides demonstrate enhanced anti-tumoral and immunomodulatory effects, inducing effective Th1 immune responses, reducing tumor proliferation, and preventing metastasis, with improved safety profiles by avoiding LPS and heparin binding, thus offering a more effective and safer cancer treatment option.
Implementation Method 1
enhancing anti-tumoral and immunomodulatory effects while promoting a Th1 immune response
Implementation Method 2
inducing effective Th1 immune responses, reducing tumor proliferation
Data Source
Figure 1A
Figure 1B~3A
Figure 3B~4A
AI summary
The present invention is related to the development of peptides derived from the sequence HYRIKPTFRRLKWKKYKGKFW, showing aminoacids substitutions, these peptides unable to bind to the lipopolysaccharide and bearing anti-tumoral and immunomodulatory capacities. These peptides alone or in combination are useful to treat cancer, and also in synergy with conventional therapies.