Researchers observed that transduced ribosomal protein S19 (Rps19)-deficient bone marrow cells could reconstitute mice longterm and rescue the bone marrow failure and severe anemia observed in Rps19-deficient mice, with a low risk of mutagenesis and a highly polyclonal insertion site pattern.
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Using the structure provided by the well-described cancer–immunity cycle, scientists outline the key steps required for a successful antitumour immune response in the context of renal cell carcinoma, and describe the development of promising new immunotherapies within the context of this framework.
[Nature Reviews Clinical Oncology]
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Scientists present an overview of nanomaterials that have been used to overcome clinical barriers to T-cell-based immunotherapies and provide their outlook of this emerging field at the interface of cancer immunotherapy and nanomaterial design.
Pfizer Inc. announced that the first participant has been dosed in the Phase III CIFFREO study, which will evaluate the efficacy and safety of investigational gene therapy candidate PF-06939926 in boys with Duchenne muscular dystrophy.
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To target both B cell Non-Hodgkin’s lymphoma and follicular T helper cells in the tumor microenvironment, researchers applied a chimeric antigen receptor that recognized human CXCR5 with high avidity.
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Bunse, M., Pfeilschifter, J., Bluhm, J., Zschummel, M., Joedicke, J. J., Wirges, A., Stark, H., Kretschmer, V., Chmielewski, M., Uckert, W., Abken, H., Westermann, J., Rehm, A., & Höpken, U. E. (2021). CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells. Nature Communications, 12(1), 240. https://doi.org/10.1038/s41467-020-20488-3 Cite
The authors review the state of currently achievable epigenetic manipulations along with corresponding applications. With future optimization, CRISPR-based epigenomic editing stands as a set of powerful tools for understanding and controlling biological function.
[Nature Cell Biology]
Researchers employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo.
[Cellular & Molecular Immunology]
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Guo, H., Chang, Y.-J., Hong, Y., Xu, L.-P., Wang, Y., Zhang, X.-H., Wang, M., Chen, H., Chen, Y.-H., Wang, F.-R., Wei-Han, Sun, Y.-Q., Yan, C.-H., Tang, F.-F., Mo, X.-D., Liu, K.-Y., & Huang, X.-J. (2021). Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation. Cellular & Molecular Immunology, 1–14. https://doi.org/10.1038/s41423-020-00597-1 Cite
Scientists showed that gene editing of Ube3a-ATS in the mouse brain resulted in the formation of base pair insertions/deletions in neurons and the subsequent unsilencing of the paternal Ube3a allele in neurons, which partially corrected the behavior phenotype of a murine Angelman syndrome model.
[Journal of Clinical Investigation]
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Researchers developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to acute myeloid leukemia.
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Benmebarek, M.-R., Cadilha, B. L., Herrmann, M., Lesch, S., Schmitt, S., Stoiber, S., Darwich, A., Augsberger, C., Brauchle, B., Rohrbacher, L., Oner, A., Seifert, M., Schwerdtfeger, M., Gottschlich, A., Rataj, F., Fenn, N. C., Klein, C., Subklewe, M., Endres, S., … Kobold, S. (2021). A modular and controllable T cell therapy platform for acute myeloid leukemia. Leukemia, 1–15. https://doi.org/10.1038/s41375-020-01109-w Cite
Using a novel conditional U2af1 knockout allele, investigators found that deletion of U2af1 results in profound defects in hematopoiesis characterized by pancytopenia, ablation of hematopoietic stem/progenitor cells leading to bone marrow failure and early lethality in mice.
As acute myeloid leukemia (AML) primary blasts express different levels of accessory protein of the interleukin-1 receptor (IL-1RAP), scientists modeled transduction of different AML tumor cell lines screened for density of antigenic sites with their lentiviral vectors carrying a third-generation IL-1RAP chimeric antigen receptor, an iCASP9 suicide gene, and a truncated CD19 surface gene.
[Cancer Gene Therapy]
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Warda, W., Da Rocha, M. N., Trad, R., Haderbache, R., Salma, Y., Bouquet, L., Roussel, X., Nicod, C., Deschamps, M., & Ferrand, C. (2021). Overcoming target epitope masking resistance that can occur on low-antigen-expresser AML blasts after IL-1RAP chimeric antigen receptor T cell therapy using the inducible caspase 9 suicide gene safety switch. Cancer Gene Therapy, 1–11. https://doi.org/10.1038/s41417-020-00284-3 Cite