IL-10-Producing CD4+ T Cells for Pure Tumor-Targeted GvT
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Solution Overview
Problem
Existing Tr1-based immunotherapy protocols for Graft-versus-Host-Disease (GvHD) and tumor treatment contain contaminant cell populations that limit their efficacy, necessitating a pure, high IL-10-producing CD4+ T cell population for targeted therapy.
Innovation Solution
Generation of a homogeneous CD4+ T cell population (CD4IL-10) through lentiviral vector-mediated gene transfer to express high levels of IL-10, which specifically targets cells expressing CD13, CD54, and HLA-class I, while maintaining anti-tumor and anti-leukemic effects without inducing GvHD.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Tr1-based immunotherapy protocols are used for GvHD and tumor treatment, then immune suppression and tumor targeting are achieved, but contaminant cell populations limit therapeutic efficacy
Solution Approach 1:
The patent extracts and isolates the desired Tr1 cells from contaminant populations through magnetic bead-based selection methods targeting specific surface markers (CD4, CD25, CD127, FoxP3), thereby obtaining a pure cell population for therapy while removing unwanted cell types that limit efficacy
Solution Approach 2:
The patent uses magnetic beads coated with antibodies as an intermediary tool to selectively bind and separate Tr1 cells from other cell populations based on their surface marker expression patterns, enabling high-purity isolation without direct cell-to-cell contact
2Productivity
If CD4+ T cells are engineered to produce high levels of IL-10, then anti-tumor and anti-leukemic effects are enhanced, but risk of immune suppression and GvHD induction increases
Solution Approach 1:
The patent engineers IL-10 production to be locally controlled and conditionally activated only in the presence of tumor or leukemia cells through promoter elements responsive to tumor microenvironment signals, ensuring IL-10 is produced where needed without causing systemic immune suppression
Solution Approach 2:
The patent modifies the IL-10 production parameters by using inducible promoter systems and regulated expression constructs that allow dynamic control of IL-10 levels based on tumor burden and treatment phase, optimizing anti-tumor efficacy while minimizing immunosuppressive side effects
3Object-affected harmful factors
If polyclonal non-Ag-specific Tregs are administered, then GvHD prevention is achieved, but tumor targeting specificity is lost
Solution Approach 1:
The patent segments the Treg population into functionally distinct subsets with different specificities by isolating Tr1 cells that recognize specific tumor-associated antigens while maintaining regulatory functions, thereby achieving both GvHD prevention and tumor-targeting capability simultaneously
Solution Approach 2:
The patent creates Tr1 cells with multi-functional capabilities that can both suppress alloreactive T cells to prevent GvHD and recognize tumor-specific antigens to provide targeted anti-tumor immunity, combining previously mutually exclusive functions in a single cell type
Data Source
AI summary
The present invention relates to a CD4+ T cell that produces high levels of IL-10 for use in the treatment and/or prevention of a tumor that expresses CD13, HLA-class I and CD54 and/or for use in inducing Graft versus tumour (GvT). The present invention relates also to a composition comprising said cell and to a method to select a subject to be treated with said cell.