Allogeneic CTL Therapy Using EBV Peptide Targeting in Autoimmune Disease
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Solution Overview
Problem
Autoimmune diseases such as multiple sclerosis (MS), systemic autoimmune diseases (SAD), and inflammatory bowel disease (IBD) are caused by abnormal immune responses against the body's own tissue, with Epstein Barr Virus (EBV) playing a predisposing role, and existing treatments are inadequate.
Innovation Solution
Administering allogeneic cytotoxic T cells (CTLs) expressing a T cell receptor that specifically binds to EBV peptides presented on class I MHC, generated by incubating CTLs with antigen-presenting cells (APCs) to induce proliferation, and selecting CTLs for compatibility with the subject's HLA allele.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for autoimmune diseases, then treatment is provided, but the treatments are inadequate and do not effectively address the underlying cause
Solution Approach 1:
The patent applies preliminary action by pre-expanding and activating allogeneic CTLs ex vivo before administration to patients. The CTLs are incubated with EBV peptides and antigen-presenting cells to induce proliferation and activation prior to in vivo administration, ensuring they are fully prepared to immediately target and eliminate EBV-infected B cells upon introduction into the patient's system.
2Reliability
If allogeneic CTLs are administered to treat autoimmune diseases, then the immune response to EBV-infected cells is enhanced, but the complexity of generating and selecting compatible CTLs increases
Solution Approach 1:
The patent uses an intermediary approach by employing antigen-presenting cells (APCs) as mediators during the ex vivo expansion process. APCs are incubated with EBV peptides to present antigens to allogeneic CTLs, facilitating their activation and proliferation. This intermediary system simplifies the selection process by using HLA allele compatibility matching between donor CTLs and recipient patients.
Solution Approach 2:
The patent applies universality by developing a standardized ex vivo expansion protocol that can be applied to multiple patients with different autoimmune diseases. The method uses universal EBV peptides (LMP1, LMP2A, EBNA1) and can select CTLs based on HLA allele compatibility, making the therapy broadly applicable across different patient populations rather than requiring patient-specific customization.
3Reliability
If EBV-infected B cells are not eliminated, then autoimmune disease progression continues, but the body's own immune cells degrade myelin and attack body tissue
Solution Approach 1:
The patent converts the harmful presence of EBV-infected B cells into a beneficial therapeutic opportunity. By using allogeneic CTLs specifically activated against EBV peptides, the therapy targets and eliminates the EBV-infected B cells that are driving autoimmune pathology. This selective elimination removes the source of autoimmune activation without requiring broad immunosuppression, thereby stopping disease progression while preserving healthy tissue.
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 method effectively treats autoimmune diseases by enhancing the immune response to target EBV-infected cells, reducing disease symptoms and progression.
Implementation Method 1
the method comprises incubating a sample comprising allogeneic CTLs with antigen presenting cells (APCs) presenting an EBV peptide on a class I MHC, thereby inducing proliferation peptide-specific CTLs in the sample
Implementation Method 2
allogeneic cytotoxic T cells (CTLs) expressing a T cell receptor that specifically binds to an EBV peptide presented on a class I MHC
Data Source
AI summary
Provided herein are compositions and methods related to the treatment of an autoimmune disease in a subject.