Description
In patients, poor persistence and function of adoptively transferred cells are major obstacles for T cell-based tumor therapies. St. Jude researchers demonstrated that by knocking out REGNASE-1, which is identified in an in vivo CRISPR discovery platform, CD8 T cell long-term persistence is greatly improved (up to 2000x), and these cells are resistant to functional exhaustion and retain robust effector function. Strikingly, REGNASE-1 deficient CD8 T cells have greatly improved ability in controlling both solid and blood cancers; making it useful in engineered T cell, including CAR-T cell, based tumor immune therapy, and potentially, regulatory T cell (Treg) based immune therapy in autoimmune diseases. Additional factors were identified to act alone or in combination with REGNASE-1 deletion to improve T-cell function. The researchers also discovered that by overexpressing one single molecular (BATF; Basic Leucine Zipper ATF-Like Transcription Factor), the accumulation and effector function of tumor-specific T cells are markedly enhanced. This is useful for immunotherapy against solid and blood cancers using CAR-T and other engineered T cells. |
Keywords
adoptive T cell cancer therapy, CAR-T, REGNASE-1, Basic Leucine Zipper ATF-Like Transcription Factor (BATF), long-term persistence, effector function, solid tumor, blood cancer, autoimmune diseases, CRISPR
Granted Patents or Published Applications
Related Scientific References
The paper is online now. https://www.nature.com/articles/s41586-019-1821-z
It is also selected by News and Views in Nature https://www.nature.com/articles/d41586-019-03731-w
News media:
https://phys.org/news/2019-12-reprogram-cells-cancer-immunotherapy.html and https://www.longroom.com/discussion/1731788/researchers-reprogram-t-cells-to-improve-cancer-immunotherapy
A broader background article: https://www.stjude.org/media-resources/news-releases/2019-medicine-science-news/reprogrammed-t-cells-improve-cancer-immunotherapy.html
Licensing Opportunities
More information is available under a confidentiality agreement. Contact chad.riggs@stjude.org
Related Links
- Activation of Prodrugs by Carboxylesterase (SJ-98-0001)
- Anti-GD2-BB-zeta Chimeric Receptor for Treating GD2+ Malignancies (SJ-13-0035)
- Antibodies to Tim4 for use as an Immune Enhancer and Cancer Therapeutic (SJ-18-0006)
- Association of Neuraminidase Regulated Exocytosis with Cancer Metastasis (SJ-11-0012)
- BCRP/ABCG2 as Stem Cell Marker (SJ-97-0016)
- CD33 CAR (SJ-17-0010)
- CD7 CAR placed in CD7neg memory cells (SJ-15-0020)
- Chimeric gene and protein that can be used to create Optogranules: Light induced stress granules (SJ-18-0010)
- Development and Optimization of a Serotype-Independent Method of Adeno-Associated Virus (AAV) Harvest and Purification (SJ-16-0036)
- DNA Methylation Profile and Biomarkers for identifying functional T-cells (SJ-17-0002)
- DNMT3a knockout CAR T cells with Antigen Specificity (for solid tumors) (SJ-19-0024)
- Efficient generation of T-Cell Receptor (TCR) sequences in response to a variety of immune responses (SJ-19-0017)
- Erythroid Specific Promoter for Hematopoietic Disorders (SJ-16-0040)
- Gene Therapy for Wiskott-Aldrich Syndrome (SJ-19-0012)
- Generation of Therapeutic T Cell Receptors for Fibrolamellar Cancer (SJ-19-0046)
- HMGA2 in Gene Therapy Vectors (SJ-16-0014)
- Hybrid Compounds to treat Gastrointestinal Infections (SJ-14-0019/UTA 14-01)
- IL35 Receptor (SJ-08-0039)
- Immune Cells with DNMT3A Gene Modifications (SJ-16-0009)
- Improved GD2 Ab for Neuroblastoma (SJ-17-0017)
- Improved Method to Produce Proteins to Treat Lysosomal Storage Disorders (SJ-01-0020)
- Interleukin-35 (IL-35) (SJ-06-0016)
- Method for Enhancing Recombinant Antibody Production (SJ-08-0032)
- Method for predicting T-cell development stage (and therapy success) (SJ-19-0033)
- Minimized Liver Specific Promoter for Improved Gene Expression in Gene Therapy Vectors (SJ-04-0024)
- miRNAs for Treating Cerebral Ventricle Enlargement in Schizophrenia Patients (SJ-19-0039)
- Myd88 and CD40 Costimulatory Domains for Chimeric Antigen Receptors (SJ-18-0021)
- New Method for Differentiating T-cells (SJ-18-0019)
- p53 Inhibitory Oligonucloeotides (SJ-09-0015)
- Protease Serine 21 (PRSS21) Targeted Immunotherapies (SJ-18-0043)
- Rapid Cloning of T Cell Receptors (SJ-16-0001)
- Regulating p53 Translation and Function (SJ-05-0002)
- RIPK3 Fusion Protein for Treating Cancer and Autoimmunity (SJ-12-0036)
- Safety Test for Gene Therapy Vectors (SJ-15-0027)
Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.