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 is a CRO & CDMO technology company that specializes in packaging recombinant adeno-associated virus (rAAV) vectors. Since its establishment in 2014, PackGene has been a leader in the AAV vector CRO service field, providing tens of thousands of custom batches of AAV samples to customers in over 20 countries. PackGene offers a one-stop CMC solution for the early development, pre-clinical development, clinical trials, and drug approval of rAAV vector drugs for cell and gene therapy (CGT) companies that is fast, cost-effective, high-quality, and scalable. Additionally, the company provides compliant services for the GMP-scale production of AAVs and plasmids for pharmaceutical companies, utilizing five technology platforms, including the π-Alpha 293 cell AAV high-yield platform and the π-Omega plasmid high-yield platform. PackGene's mission is to make gene therapy affordable and accelerate the launch of innovative gene drugs. The company aims to simplify the challenging aspects of gene therapy development and industrialization processes and provide stable, efficient, and economical rAAV Fast Services to accelerate gene and cell therapy development efforts from discovery phase to commercialization.
Related News
Another Two-Plasmid AAV Gene Therapy Enters Clinical Trial: Gene Vector Biotechnology’s JWK001 Pioneers in Treating nAMD
On November 30, 2023, Gene Vector Biotechnology Co., Ltd. in Chengdu, China, received approval from the National Medical Products Administration's Center for Drug Evaluation (CDE) for the clinical trial of JWK001, a Class I gene therapy drug for treating neovascular...
Accelerating Gene Therapy Production: Combining next-generation AAV vectors and artificial intelligence (AI)
Recently, the France-based WIDGeT consortium emerged from a collaboration between Sanofi, WhiteLab Genomics, the TaRGeT Laboratory at Nantes University, and Institut Imagine. Scientists and companies in this consortium hope to speed up the development of gene...
REGENXBIO Announces Dose Escalation in AFFINITY DUCHENNE® Trial
First patient received dose level 2 of RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin On track for pivotal dose determination and initiation of pivotal program in 2024...
FDA is investigating whether CAR-T, a cancer therapy pioneered at Penn, can cause lymphoma
Hodgkin lymphoma, nodular lymphocyte predominant (high-power view) Credit: Gabriel Caponetti, MD./Wikipedia/CC BY-SA 3.0The University of Pennsylvania plans to continue offering CAR-T therapy, a cancer treatment pioneered at Penn, after the Food and Drug...
