Bi-Specific CAR T Cells With CMV Vaccination for Better Persistence

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Solution Overview

Problem

Existing tumor-specific T cell therapies face challenges with insufficient persistence and low tumor-specificity, limiting their long-term anti-tumor efficacy.

Innovation Solution

Development of bi-specific T cells transduced with a chimeric antigen receptor (CAR) specific for CMV and a tumor antigen, such as CD19, combined with CMV peptide vaccination to enhance T cell proliferation and anti-tumor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional T cell therapy is used, then tumor-specificity is achieved, but persistence and long-term anti-tumor functioning are insufficient

Engineering Contradiction:

Improvetumor-specificityVSAvoidpersistence

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent combines two different T cell populations - virus-specific T cells (enriched for CMV-specificity) and tumor-targeting CAR T cells - into a single bi-specific T cell product. This merging allows the cells to maintain tumor-specificity through the CAR component while gaining enhanced persistence through the virus-specific T cell component, which exhibits better in vivo survival characteristics.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The bi-specific T cells are engineered to perform multiple functions simultaneously: they retain the ability to recognize and respond to viral antigens (CMV) through their TCR while also targeting tumor antigens (such as CD19, CD123, or HER2) through the CAR. This multi-functionality enables the cells to leverage both virus-specific persistence mechanisms and tumor-specific targeting capabilities.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If CAR T cell therapy is used, then tumor targeting is improved, but in vivo persistence is attenuated

Engineering Contradiction:

Improvetumor targetingVSAvoidin vivo persistence

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent merges CAR T cells with virus-specific T cells to create bi-specific T cells that combine the tumor-targeting capability of CAR T cells with the enhanced persistence of virus-specific T cells. The virus-specific component provides better in vivo survival while the CAR ensures accurate tumor targeting.

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If high dose T cell therapy is administered, then anti-tumor activity is enhanced, but cell dose requirements increase treatment complexity

Engineering Contradiction:

Improveanti-tumor activityVSAvoidcell dose

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The bi-specific T cells are designed to self-proliferate in vivo by leveraging the virus-specific component's ability to recognize viral antigens (such as CMV) that may be present in the tumor microenvironment or administered as a vaccine. This self-service proliferation mechanism reduces the need for high initial cell doses and minimizes the need for external support therapies.

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS20260015404A1Bi-specific targeted chimeric antigen receptor t cells

Publication Date: 2026.01.15 CITY OF HOPE

AI summary

T cells expressing a chimeric antigen receptor and a T cell receptor specific for CMV (bi-specific T cells) are described as a methods for using such cells in immunotherapy. In the immunotherapy methods, the recipient can be exposed to a CMV vaccine in order to expand and/or stimulate the be-specific T cells.