Postbiotic Composition for HLA Class I Upregulation in Tumors
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Solution Overview
Problem
Existing cancer treatments, particularly immune checkpoint inhibitor (ICI)-based therapies, face challenges due to tumour cells evading immune recognition through reduced expression of HLA class I, leading to immune escape mechanisms.
Innovation Solution
The use of postbiotics derived from Lactobacillus paracasei CNCM 1-5220 fermentation supernatant to upregulate HLA class I expression on tumour cells, enhancing TA-specific CTL responses and sensitizing tumour cells to ICI treatment, potentially combined with anti-PD-1 antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitor (ICI) therapy is used to treat cancer, then immune recognition of tumour cells is enhanced, but tumour cells with reduced HLA class I expression evade immune recognition and cause treatment failure
Solution Approach 1:
The patent applies parameter changes by using postbiotics to modify the expression level of HLA class I molecules on tumour cells. The postbiotics induce upregulation of HLA class I, thereby changing the immunogenicity parameter of tumour cells and making them more recognizable to CTLs, which resolves the immune escape problem and enhances ICI therapy efficacy.
2Reliability
If postbiotics are used to upregulate HLA class I expression on tumour cells, then immune recognition is enhanced, but the mechanism of action requires elucidation
Solution Approach 1:
The patent employs feedback by demonstrating that postbiotics activate the NF-κB signaling pathway, which in turn upregulates HLA class I expression. This creates a feedback loop where the postbiotics induce a cellular response that amplifies the desired effect (HLA class I upregulation), thereby enhancing immune recognition while providing insight into the molecular mechanism through pathway activation.
3Adaptability or versatility
If tumour cells reduce HLA class I expression to evade immune detection, then immune escape is achieved, but therapeutic response to ICI is lost
Solution Approach 1:
The patent applies preliminary anti-action by administering postbiotics before ICI therapy to preemptively upregulate HLA class I expression on tumour cells. This preliminary action counteracts the tumour cells' adaptive immune escape mechanism, ensuring that when ICI therapy is administered, the tumour cells are already in a state of high HLA class I expression and thus more susceptible to immune recognition and destruction.
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 postbiotics increase HLA class I expression on tumour cells, potentiating immune recognition and controlling tumour growth, prolonging survival in murine models, and demonstrating safety and efficacy in combination with ICI therapies.
Implementation Method 1
postbiotics derived from Lactobacillus paracasei CNCM 1-5220 fermentation supernatant
Data Source
AI summary
Methods of treatment and/or prevention of tumours, preferably of solid tumours, more preferably of breast cancer, melanoma, bladder cancer, head and neck cancer, Hodgkin's lymphoma, kidney cancer, non-small cell lung cancer using fermented supernatant, or fractions thereof, of the Lactobacillus casei or paracasei species are disclosed. The species is the strain deposited according to the Budapest Treaty with No. CNCM I-5220 and/or includes in its DNA genome a DNA sequence essentially identical to one of: SEQ ID No 1 to 5.