NTB-A Ectodomain T Cell Expansion Without IL-2 Toxicity

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current immunotherapy approaches for cancer treatment, particularly those involving T cell modulation, face challenges such as T cell apoptosis, reduced responsiveness due to cytokine down-regulation, and high toxicity of exogenous cytokines like IL-2.

Innovation Solution

The use of an exogenously added polypeptide corresponding to the extracellular domain of human NTB-A (NTB-A ectodomain) to protect T cells from apoptotic cell death, enhance cytotoxicity, and promote interferon-gamma production and surface CD137 expression, thereby improving T cell activation and expansion without the need for IL-2.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If exogenous cytokines like IL-2 are used to promote T cell activation and expansion, then T cell proliferation is enhanced, but toxicity increases and T cell responsiveness is reduced due to cytokine down-regulation

Engineering Contradiction:

ImproveT cell proliferationVSAvoidtoxicity and cytokine down-regulation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an exogenously added NTB-A polypeptide as an intermediary molecule to activate T cells through homotypic interactions. This mediator bypasses the need for exogenous IL-2 cytokines, achieving T cell activation and expansion without the associated toxicity and cytokine down-regulation problems. The NTB-A polypeptide acts as a substitute signaling molecule that triggers T cell responses through a different pathway.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If T cells are activated using conventional methods, then T cell expansion is achieved, but T cell apoptosis occurs and survival is reduced

Engineering Contradiction:

ImproveT cell expansionVSAvoidT cell survival

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by adding the NTB-A polypeptide before and during T cell activation processes. This pre-treatment with NTB-A prepares the T cells for activation while protecting them from apoptosis. The polypeptide is present during the activation process to ensure both expansion and survival, preventing cell death before it can occur.

Inventive Principle:

Principle #10Preliminary action

3Object-affected harmful factors

If NTB-A fusion protein is used as antagonist to inhibit Th1 responses, then autoimmune disease is inhibited, but anti-tumor efficacy is reduced

Engineering Contradiction:

Improveautoimmune disease inhibitionVSAvoidanti-tumor efficacy

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent inverts the approach by using NTB-A as an agonist rather than an antagonist. Instead of blocking NTB-A interactions to suppress Th1 responses, the invention uses exogenously added NTB-A polypeptide to actively stimulate T cell responses. This inversion of the therapeutic strategy enables anti-tumor efficacy while avoiding the suppression of beneficial immune responses.

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentEP3091999B2Improved cell compositions and methods for cancer therapy

Publication Date: 2025.05.07 HADASIT MEDICAL RESEARCH SERVICES & DEVELOPMENT LTD

Figure 1A~1B
Figure 2A
Figure 2B

AI summary

The present invention is directed to the field of immunotherapy. Specifically, the invention provides compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the invention are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.