CRISPR-mediated deletion of the Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) improves human T cell function for adoptive T cell therapy
Prade, S.; Wright, D.; Logan, N.; Teagle, A. R.; Stauss, H. J.; Zamoyska, R.
Show abstract
Adoptive T cell transfer has improved the treatment of cancer patients. However, treatment of solid tumors is still challenging and new strategies that optimize T cell function and response duration in the tumor could be beneficial additions to cancer therapy. In this study, we deleted the intracellular phosphatase PTPN22 and the endogenous TCR chain from human PBMC-derived T cells using CRISPR/Cas9 and transduced them with TCRs specific for a defined antigen. Deletion of PTPN22 in human T cells increased the secretion of IFN{gamma} and GM-CSF in multiple donors. The cells retained a polyfunctional cytokine expression after re-stimulation and greater numbers of PTPN22KO T cells expressed inflammatory cytokines compared to unmutated control cells. PTPN22KO T cells seemed to be more polyfunctional at low antigen concentrations. Additionally, we were able to show that that PTPN22KO T cells were more effective in controlling tumor cell growth. This suggests that they might be more functional within the suppressive tumor microenvironment thereby overcoming the limitations of immunotherapy for solid tumors.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Human T cells employ conserved AU-rich elements to fine-tune IFN-γ production 96%
- Identification and Structural Characterization of a mutant KRAS-G12V specific TCR restricted by HLA-A3 95%
- Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response against the AH1 tumor rejection antigen 95%
Similar papers in this journal
- Domain Binding and Isotype Dictate the Activity of Anti-human OX40 Antibodies 95%
- Genome-wide CRISPR/Cas9 screen reveals factors that influence the susceptibility of tumor cells to NK cell-mediated killing 94%
- HERV-derived epitopes represent new targets for T-cell based immunotherapies in ovarian cancer 94%
Similar papers in this journal
- CD4+ tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts 95%
- CD20 expression regulates CD37 levels in B-cell lymphoma: implications for immunotherapies. 95%
- CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade 93%
Similar papers in this journal
- IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors 94%
- Rapid generation of CD19 CAR-T Cells by minicircle DNA enables anti-tumor activity and prevents fatal CAR-B leukemia 93%
- Anaplastic Thyroid Cancer Cells Upregulate Mitochondrial One-Carbon Metabolism To Meet Purine Demand, Eliciting A Critical Targetable Vulnerability 92%
Similar papers in this journal
- Antigenic determinants of SARS-CoV-2-specific CD4 + T cell lines reveals M protein-driven dysregulation of interferon signaling 95%
- Exploration of T-cell immune responses by expression of a dominant-negative SHP1 and SHP2 94%
- T-cell receptors identified by a personalized antigen-agnostic screening approach target shared neoantigen KRAS Q61H 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.