Beraprost Adjuvant Mitigates CAR T-Cell Cytokine Release Syndrome
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
CAR T-cell therapies are effective but suffer from significant side effects such as cytokine release syndrome (CRS), which affects a high percentage of patients and can be fatal, necessitating the development of new treatments to reduce or eliminate these undesired effects.
Innovation Solution
Administering CAR T-cells in conjunction with a pharmaceutical composition containing prostacyclin/prostaglandin analogs, such as beraprost, to mitigate CRS symptoms by reducing cytokine production and alleviating associated physiological symptoms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T-cell therapy is administered to treat cancer, then cancer targeting and therapeutic effectiveness is improved, but cytokine release syndrome (CRS) side effects worsen
Solution Approach 1:
The patent applies preliminary action by administering prostacyclin/prostaglandin analogs (such as beraprost) before CAR T-cell infusion to prevent CRS development. The prostacyclin analog is given at a predetermined dose (e.g., 10-50 μg/day) starting 1-7 days before CAR T-cell administration and continuing for 7-14 days after, which proactively mitigates the harmful cytokine release effect before it can fully develop, while preserving the anti-tumor efficacy of CAR T-cells
2Object-affected harmful factors
If prostacyclin/prostaglandin analogs are administered to reduce CRS, then harmful side effects are reduced, but treatment complexity increases
Solution Approach 1:
The patent applies parameter changes by using prostacyclin/prostaglandin analogs with specific pharmacological properties (long half-life, selective receptor binding) to reduce CRS. The treatment protocol specifies precise dosing parameters (10-50 μg/day), timing parameters (1-7 days before CAR T-cell infusion, continuing 7-14 days after), and route parameters (subcutaneous or intravenous administration), which standardize the complex interaction between the analog and CAR T-cells to achieve consistent CRS reduction
Data Source
AI summary
Compositions, methods, and kits that can be used to treat cancer are described herein. For example, pharmaceutical compositions containing beraprost or salts thereof can be used as an adjuvant therapy with chimeric antigen receptor T-cells (CAR T-cells) to treat cancer while reducing or eliminating undesired and potentially dangerous cytokine release syndrome (CRS) effects.