Researchers at Duke University have advanced cancer T-cell therapy using CRISPR for high-throughput screening of human immune cells. They discovered BATF3, a master regulator transcription factor gene, which reprograms thousands of genes in T cells, enhancing their ability to destroy cancer cells. This breakthrough could amplify the efficacy of existing and developing T-cell therapies and extend their application to other diseases like autoimmune disorders.
Sean McCutcheon, co-lead author, notes that T cells often become ‘tired’ and lose their cancer-fighting ability. The team’s approach aims to strengthen T cells by mimicking successful naturally occurring cell states. The study, led by Charles Gersbach and reported in Nature Genetics, explores transcriptional and epigenetic regulators in human CD8+ T cells.
Adoptive T-cell therapy (ACT), a decade-old cancer treatment method, involves genetically engineered T cells targeting cancer cells. However, its effectiveness against solid tumors is limited due to physical barriers and T-cell exhaustion. Gersbach’s lab developed a CRISPR-Cas9 method to modulate genes without cutting them, focusing on the “dark genome” areas that change as T cells transition between states.
Their screening identified 120 master regulator genes affecting T-cell function. BATF3 emerged as a key gene, enhancing T cells’ potency and resistance to exhaustion. Tests showed that BATF3 overexpression in T cells led to their improved performance against human breast cancer tumors in a mouse model.
The methodology’s broader impact lies in its potential to identify and modulate master regulators, improving therapeutic performance. This approach allows profiling master regulators using various T cell sources or cancer models, representing a significant advancement in making T-cell therapy more effective for more patients and cancer types.
McCutcheon’s further studies on BATF3, involving CRISPR knockout screens of over 1,600 gene expression regulators, revealed new factors for enhancing T-cell therapy. This catalog of genes opens avenues for developing next-generation cancer immunotherapies, potentially enabling patient-specific or generalized T cells for a wide range of cancers.
Reference:
McCutcheon, S.R., Swartz, A.M., Brown, M.C. et al. Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens. Nat Genet (2023). https://doi.org/10.1038/s41588-023-01554-0
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
Related News
NeuExcell Therapeutics Unveils Breakthrough in Stroke Treatment at ASGCT 2024
In a groundbreaking development, NeuExcell Therapeutics has revealed a significant breakthrough in its NXL-001 product for stroke treatment. The announcement was made at the 2024 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, where the company...
Unraveling CRISPR Precision: BreakTag Illuminates Pathways to Improved Gene Editing
Introduction:The quest for precision in CRISPR-Cas9 gene editing takes a significant leap forward with the development of BreakTag, a method devised to enhance our understanding of DNA double-strand breaks (DSBs) induced by Cas9. This breakthrough, detailed in a...
Sumitomo Pharma Announces FDA Acceptance of Supplemental New Drug Application for Vibegron in Men with Overactive Bladder Symptoms Receiving Pharmacological Therapy for Benign Prostatic Hyperplasia
–Supplemental New Drug Application (sNDA) submission based on Phase 3 study of vibegron 75mg (GEMTESA) demonstrating statistically significant reductions in daily micturition and urgency episodes– –If approved, vibegron will be the first and only beta-3 agonist for...
Herpes cure with gene editing makes progress in laboratory studies
Herpes simplex virus. Credit: CDCResearchers at Fred Hutch Cancer Center have found in pre-clinical studies that an experimental gene therapy for genital and oral herpes removed 90% or more of the infection and suppressed how much virus can be released from an...
Related Services
