Vβ17+CD8+ T Cell Engagers for Solid Tumors

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Solution Overview

Problem

Current CD3 bispecific T cell engagers for cancer therapy face challenges such as immune-related adverse events (IRAEs) due to pan-activation of T cells, cytokine storms, and limited efficacy in solid tumors due to inefficient T cell recruitment and penetration.

Innovation Solution

Development of a pharmaceutical composition comprising Vβ17+CD8+ T cells activated by M1 peptide from influenza A virus and IL-2, combined with multispecific T cell engagers that target tumor-associated antigens, to redirect T cells to cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CD3 bisspecific T cell engagers are used to activate T cells for cancer therapy, then T cell activation and tumor killing capacity are improved, but immune-related adverse events and cytokine storms occur due to pan-activation of T cells

Engineering Contradiction:

ImproveT cell activation efficacyVSAvoidimmune-related adverse events and cytokine storms

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by shifting from pan-T cell activation to selective activation of specific T cell subsets (Vβ17+CD8+ T cells, γδ T cells, or NKT cells) through bispecific engagers targeting specific TCR Vβ regions. This localized activation approach maintains therapeutic efficacy while reducing off-target immune activation and associated adverse events.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the activation parameter from broad CD3-mediated pan-T cell activation to specific Vβ region-targeted activation. By altering the target parameter from CD3 to specific TCR Vβ regions (e.g., Vβ17), the system achieves selective T cell subset activation, improving the therapeutic index by reducing cytokine storm while maintaining anti-tumor efficacy.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If CD3 bisspecific T cell engagers are used to recruit T cells to tumors, then T cell cytotoxicity is enhanced, but efficacy in solid tumors is limited due to inefficient T cell recruitment and penetration

Engineering Contradiction:

ImproveT cell cytotoxicityVSAvoidT cell recruitment and penetration efficiency

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies local quality by targeting specific T cell subsets (Vβ17+CD8+ T cells, γδ T cells, or NKT cells) with enhanced tissue-penetrating capabilities rather than relying on pan-T cell recruitment. This selective approach improves penetration into solid tumor microenvironments while maintaining cytotoxic efficacy.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs dynamic selection of different T cell subsets (Vβ17+CD8+ T cells, γδ T cells, or NKT cells) depending on the specific tumor type and clinical context. This dynamic approach allows optimization of T cell recruitment and penetration strategies for different solid tumor microenvironments.

Inventive Principle:

Principle #15Dynamics

Data Source

PatentUS20250205280A1Methods and Compositions Comprising V beta 17 Bispecific T Cell Engagers and Bioengineered Virus Specific Lymphocytes

Publication Date: 2025.06.26 JANSSEN BIOTECH INC

AI summary

Provided is a pharmaceutical composition or combination comprising: (i) an isolated population of cells comprising Vβ17+CD8+ T cells, (ii) one or more T cell engagers; and (iii) a pharmaceutically acceptable excipient. Also provided are methods of using the isolated population of cells comprising Vβ17+CD8+ T cells and the T cell engagers for redirecting a T cell to a target cell, inhibiting the growth or proliferation of a target cell, eliminating a target cell, or treating a disease or disorder.