BCG β-Glucan Adjuvant for Trained Neutrophil Cancer Immunotherapy
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Solution Overview
Problem
Current BCG immunotherapy for bladder cancer is limited by high recurrence rates, adverse effects, and non-responsiveness in 40-60% of patients, necessitating repetitive treatments and radical cystectomy, while melanoma treatment requires multiple drugs with different mechanisms due to heterogeneity.
Innovation Solution
Combining Bacillus Calmette-Guérin (BCG) vaccine with β-glucan adjuvant, particularly with a β-1,3 glucose backbone and optional β-1,6 side branching, to reprogram hematopoietic stem cells and generate trained neutrophils with antitumor capacity, preventing conversion to pro-tumor neutrophils.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If BCG immunotherapy is administered at high dose (1×10^8 CFU) and repeated (at least 12 doses during first 6 months), then complete response rate is improved, but adverse effects increase leading to intolerance in about 20% of cases
Solution Approach 1:
The patent changes the dosage parameter from high dose (1×10^8 CFU) to low dose (1×10^6 CFU), and changes the treatment frequency from repeated (12 doses) to single administration, while maintaining therapeutic effectiveness and reducing adverse effects
Solution Approach 2:
The patent introduces β-glucan as an adjuvant that mediates the immune response enhancement, allowing the BCG to work effectively at lower doses without requiring repeated administrations
2Reliability
If BCG immunotherapy is administered repeatedly (at least 12 doses during first 6 months), then treatment effectiveness is improved, but treatment complexity and patient burden increase
Solution Approach 1:
The patent changes the treatment regimen parameters from multiple doses (12 administrations) to single dose, and from high dose (1×10^8 CFU) to low dose (1×10^6 CFU), simplifying the treatment protocol while maintaining effectiveness through the addition of β-glucan adjuvant
3Reliability
If radical cystectomy is performed for non-responders, then cancer treatment is improved, but patient quality of life is severely compromised
Solution Approach 1:
The patent applies preliminary action by administering β-glucan adjuvant before BCG therapy to pre-condition the immune system, ensuring better response to the subsequent BCG treatment and avoiding the need for radical cystectomy
Solution Approach 2:
The patent introduces β-glucan as an intermediary substance that enhances the immune system's response to BCG, providing a middle-ground solution that achieves cancer treatment effectiveness without requiring the extreme measure of radical cystectomy
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 survival rates in bladder cancer models to 100% with no tumor detection, addresses non-responsiveness, and reduces adverse effects by maintaining trained neutrophils with antitumor capacity.
Implementation Method 1
reprogram hematopoietic stem cells and generate trained neutrophils with antitumor capacity
Implementation Method 2
The β-glucan has a β-1,3 glucose backbone, preferably. The β-glucan can also have β-1,6 side branching.
Data Source
AI summary
There is provided the combination of Bacillus Calmette-Guérin (BCG) vaccine and β-glucan adjuvant for the treatment of a cancer characterized by the presence of protumoral T3 neutrophils in the tumour microenvironment. The β-glucan is characterized by a μ-1,3 glucose backbone. The BCG and β-glucan combination demonstrated a synergistic effect in remodeling the tumour microenvironment to resist conversion of neutrophils into the T3 phenotype. The cancer can be bladder cancer, melanoma, lung adenocarcinoma, head and neck squamous cell cancer, pancreatic adenocarcinoma, low-grade gliomas, esophageal carcinoma, and cervical squamous cell carcinoma.