BET-Treated Tumor Cell Composition for Enhanced Antigen Presentation
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Solution Overview
Problem
Existing immunotherapies for cancer often fail to induce a clinical benefit due to immune evasion mechanisms employed by tumors, which prevent recognition of cancer antigens by the immune system, leading to ineffective anti-tumor immunity.
Innovation Solution
The use of Bromodomain and Extra-Terminal domain (BET) inhibitors to enhance interferon-gamma signaling, increase antigen presentation, and suppress immunosuppressive pathways in tumor cells, thereby improving their immunogenicity and responsiveness to immune therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tumor cells are used as immunogenic vehicles, then anti-tumor immune response is enhanced, but tumor cells fail to induce adequate T-cell response due to immune evasion mechanisms
Solution Approach 1:
The patent applies parameter changes by treating tumor cells with BET inhibitors that modulate epigenetic parameters, specifically affecting chromatin structure and gene expression. This changes the immunogenic parameters of tumor cells by increasing MHC class I expression and altering protein expression profiles, thereby overcoming immune evasion mechanisms and enhancing T-cell recognition without altering the fundamental tumor cell identity
2Reliability
If interferon-gamma signaling is enhanced to improve antigen presentation, then T-cell recognition is increased, but constitutive and interferon-gamma-induced HLA class II expression and IDO production are also induced which may suppress immunity
Solution Approach 1:
The patent applies local quality by using BET inhibitors to create localized epigenetic modifications at specific chromatin regions. This results in selective upregulation of MHC class I expression and specific protein markers while suppressing HLA class II and IDO production, achieving spatial and functional differentiation in the immune response modulation
Solution Approach 2:
The patent applies preliminary action by pre-treating tumor cells with BET inhibitors before introducing them to the immune system. This preliminary epigenetic modification prepares the tumor cells to enhance antigen presentation and suppress immunosuppressive pathways, creating a favorable immunogenic environment before actual immune interaction occurs
Data Source
AI summary
The invention relates to the field of immunotherapy, more in particular to a composition for use in the treatment of cancer. The invention also relates to a composition obtainable by such a method, such as a pharmaceutical composition. More in particular, the invention relates to an ex vivo method for obtaining a composition suitable for the treatment of cancer in a subject, comprising the steps of providing primary tumor cells derived from the subject, and ex vivo contacting the tumor cells with an inhibitor of a bromodomain and extra-terminal domain family member (BET inhibitor).