Membrane-Anchored IL-7 TILs for Tumor Persistence and Cytotoxicity

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Solution Overview

Problem

Current TIL therapy faces challenges with immunosuppressed TILs having limited tumor cytotoxic effects and persistence due to the inhibitory tumor microenvironment, and there is a need for enhanced proliferative ability and persistence of genetically modified TILs.

Innovation Solution

A modified TIL expressing membrane-anchored IL-7, comprising IL-7 or its functional fragments and a transmembrane domain, is developed, optionally with a membrane surface tag and linker, to enhance TIL activation and persistence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If TILs are cultured and expanded from solid tumor tissues, then the therapy shows excellent efficacy against solid tumors, but the immunosuppressive microenvironment inside the tumor still has an inhibitory effect on the infused TILs, limiting their activity and persistence

Engineering Contradiction:

Improvetumor cytotoxic efficacyVSAvoidpersistence duration of TILs in the body

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent introduces membrane-anchored cytokines (IL-7, IL-15, IL-21) as intermediary substances that mediate between the TILs and the immunosuppressive tumor microenvironment. These cytokines are anchored on the TIL surface to create a protective and activating microenvironment around the infused cells, counteracting the inhibitory effects of the tumor microenvironment and enhancing both activity and persistence

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The TILs are genetically modified to autonomously produce and display their own cytokines (IL-7, IL-15, IL-21) on their surface through membrane-anchored constructs. This self-service mechanism allows the TILs to create their own supportive microenvironment without external assistance, enabling sustained activation and persistence directly at the tumor site

Inventive Principle:

Principle #25Self-service

2Productivity

If TILs are genetically modified to enhance proliferative ability and tumor cytotoxic efficacy, then the therapy effectiveness is improved, but there is a need for more engineering technologies to prolong persistence of TILs in the body

Engineering Contradiction:

Improveproliferative ability of TILsVSAvoidpersistence of TILs in the body

Core Design Contradiction:

ProductivityVSDuration of action of moving object

Solution Approach 1:

The patent combines multiple cytokine functions (IL-7 for proliferation and survival, IL-15 for activation and persistence, IL-21 for differentiation and anti-apoptosis) into a single genetically modified TIL construct. This merging of multiple cytokine activities into one engineered cell type simultaneously achieves enhanced proliferation, sustained persistence, and improved tumor cytotoxic efficacy

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The TILs are engineered with composite structures including membrane-anchored cytokine constructs (comprising cytokine domains, transmembrane domains, and signaling domains), co-expression of checkpoint inhibitors (PD-1, LAG-3, TIGIT), and multiple cytokine receptors. This composite engineering approach creates TILs with enhanced and multifaceted functional properties that simultaneously improve proliferation and persistence

Inventive Principle:

Principle #40Composite materials

Data Source

PatentEP4674954A1Tumor infiltrating lymphocyte expressing membrane-bound cytokine

Publication Date: 2026.01.07 SHANGHAI JUNCELL THERAPEUTICS CO LTD

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AI summary

Provided is a tumor infiltrating lymphocyte expressing a membrane-bound cytokine, specifically a modified TIL expressing membrane-anchored IL-7. The TIL can be effectively activated and proliferated, can be efficiently detected and sorted, and can effectively mediate molecular braking.