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Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

Published on: February 16, 2015

Functional genomics for improving adoptive T-cell transfer therapies.

Joseph G Skeate^1,2,3, Chang-Jung Lee^3,4, Carli Stewart^5,6,7

¹Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.

Journal for Immunotherapy of Cancer

|December 9, 2025

Summary

Forward genetic screens using CRISPR and Sleeping Beauty transposon mutagenesis identify novel genetic targets to enhance adoptive cell therapy (ACT) effectiveness in solid tumors. These tools overcome challenges like tumor microenvironment and T-cell exhaustion, improving ACT durability.

Keywords:

Adoptive cell therapy - ACT Genome Next generation sequencing - NGS Tumor microenvironment - TME

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Area of Science:

Cancer immunotherapy
Functional genomics
Genetic engineering

Background:

Adoptive cell therapy (ACT) shows promise for leukemia but faces challenges in solid tumors.
Limitations include toxicities, immunosuppressive tumor microenvironment, and T-cell exhaustion.
Ex vivo T-cell engineering offers opportunities for genetic modification to improve ACT.

Purpose of the Study:

To summarize forward genetic screens and tools for enhancing ACT.
To identify novel genetic targets for improving ACT efficacy in solid tumors.
To explore complementary approaches for discovering translatable genetic editing strategies.

Main Methods:

Utilizing CRISPR for functional genomics and understanding resistance mechanisms.
Employing Sleeping Beauty transposon mutagenesis for discovering novel genetic edits.
Summarizing findings from forward genetic screens.

Main Results:

Forward genetic screens identify genetic targets to enhance ACT.
CRISPR and Sleeping Beauty transposon mutagenesis are key tools.
Complementary approaches can uncover strategies to overcome ACT limitations.

Conclusions:

Forward genetic screens are valuable for discovering genetic edits to improve ACT.
Combining tools like CRISPR and Sleeping Beauty enhances target identification.
Further research is needed to recapitulate disease-specific challenges for translatable strategies.