T cell activation response constructs for enhanced CAR-T cell therapy

By designing gene circuits and nucleic acid constructs containing NR4A1 response elements, the difficulty and side effects of gene expression regulation in CAR-T cell therapy are solved, and the controlled activation and efficient treatment of CAR-T cells are achieved.

CN119630801APending Publication Date: 2025-03-14RGT UNIV OF CALIFORNIA
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Patent Information

Application Number
CN202380051619.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2022-05-16
Filing Date
2023-05-15
Publication Date
2025-03-14

AI Technical Summary

Technical Problem

Existing CAR-T cell therapies have side effects on the regulation of therapeutic gene expression and are difficult to effectively regulate or turn off the activity of CAR-T cells, resulting in T cell depletion and inappropriate anti-tumor response.

Method used

A set of gene circuits and nucleic acid constructs are designed to contain response elements from the NR4A1 locus for enabling customizable gene program activation in primary human T cells. The gene circuit comprises a nucleic acid construct having a transcriptional regulatory region comprising a response element operably linked to a nucleic acid sequence of interest for activating T cells and regulating gene expression in response to CAR receptor or TCR ligation.

Benefits of technology

Through this technical means, the controlled activation of CAR-T cells and gene expression regulation are achieved, which reduces side effects, improves treatment efficiency, and allows the specific recognition and response of T cells to target antigens.

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Abstract

The present disclosure generally relates to gene circuits comprising a response element engineered from NR4A1 that increases chimeric antigen receptor activation accompanying delivery of biologically active molecules. In particular, the present disclosure provides nucleic acid constructs comprising a response element operably linked to a nucleic acid sequence of interest such that it reacts to activation of CAR-T cells. The disclosure also relates to vectors and cells comprising the gene circuit and the nucleic acid construct. Also provided are methods of inducing an immune response, methods of treating a subject, and methods for delivering a bioactive molecule through an activated T cell having a chimeric antigen receptor and a response element construct of the present disclosure.
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