Engineering CAR-T Cells for Next-Generation Cancer Therapy

Investigators highlight recent strategies to improve chimeric antigen therapy (CAR)-T cell therapy by engineering the CAR protein, T cells, and the interaction between T cells and other components in the tumor microenvironment.
[Cancer Cell]
Hong, M., Clubb, J. D., & Chen, Y. Y. (2020). Engineering CAR-T Cells for Next-Generation Cancer Therapy. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2020.07.005 Cite
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Spatiotemporal PET Imaging Reveals Differences in CAR-T Tumor Retention in Triple-Negative Breast Cancer Models

Researchers generated and characterized traceable CAR T cells and examined potential negative effects of radionuclide reporter use. They applied the platform to two different triple-negative breast cancer models and unexpectedly observed pronounced differences in CAR-T tumor retention by PET/computed tomography and confirmed data ex vivo.
[Molecular Therapy]
Volpe, A., Lang, C., Lim, L., Man, F., Kurtys, E., Ashmore-Harris, C., Johnson, P., Skourti, E., Rosales, R. T. M. de, & Fruhwirth, G. O. (2020). Spatiotemporal PET Imaging Reveals Differences in CAR-T Tumor Retention in Triple-Negative Breast Cancer Models. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2020.06.028 Cite
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Regulatory T Cells Suppress Th17 Cell Ca2+ Signaling in the Spinal Cord during Murine Autoimmune Neuroinflammation

Investigators used two-photon microscopy to elucidate the spatial organization, motility characteristics, and interactions of endogenous Treg and Th17 cells together with antigen-presenting cells within the spinal cord leptomeninges in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.
[Proceedings of the National Academy of Sciences of the United States of America]
Othy, S., Jairaman, A., Dynes, J. L., Dong, T. X., Tune, C., Yeromin, A. V., Zavala, A., Akunwafo, C., Chen, F., Parker, I., & Cahalan, M. D. (2020). Regulatory T cells suppress Th17 cell Ca2+ signaling in the spinal cord during murine autoimmune neuroinflammation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2006895117 Cite
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MSCs-Released TGFβ1 Generate CD4+CD25+Foxp3+ in T-Reg Cells of Human SLE PBMC

The authors used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities.
[Journal of the Formosan Medical Association]
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The Immunology of Renal Cell Carcinoma

Renal cell carcinoma is considered to be an immunogenic tumor but is known to mediate immune dysfunction in large part by eliciting the infiltration of immune-inhibitory cells, such as regulatory T cells and myeloid-derived suppressor cells, into the tumor microenvironment.
[Nature Reviews Nephrology]
Díaz-Montero, C. M., Rini, B. I., & Finke, J. H. (2020). The immunology of renal cell carcinoma. Nature Reviews Nephrology, 1–15. https://doi.org/10.1038/s41581-020-0316-3 Cite
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An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells

Researchers present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules.
[Cell]
da Silva, C. O., Gicquel, T., Daniel, Y., Bártholo, T., Vène, E., Loyer, P., Pôrto, L. C., Lagente, V., & Victoni, T. (2020). Alteration of immunophenotype of human macrophages and monocytes after exposure to cigarette smoke. Scientific Reports, 10(1), 12796. https://doi.org/10.1038/s41598-020-68753-1 Cite
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Microbiota-Dependent Expansion of Testicular IL-17-Producing Vγ6+ γδ T Cells upon Puberty Promotes Local Tissue Immune Surveillance

Investigators characterized a population of interleukin 17-producing γδ T cells that seeded the testis of naive C57BL/6 mice, expand at puberty and persisted throughout adulthood.
[Mucosal Immunology]
Wilharm, A., Brigas, H. C., Sandrock, I., Ribeiro, M., Amado, T., Reinhardt, A., Demera, A., Hoenicke, L., Strowig, T., Carvalho, T., Prinz, I., & Ribot, J. C. (2020). Microbiota-dependent expansion of testicular IL-17-producing Vγ6 + γδ T cells upon puberty promotes local tissue immune surveillance. Mucosal Immunology, 1–11. https://doi.org/10.1038/s41385-020-0330-6 Cite
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LRCH1 Deficiency Enhances LAT Signalosome Formation and CD8+ T Cell Responses against Tumors and Pathogens

Investigators demonstrated that LRCH1 directly bound linker for activation of T cells (LAT), reduced LAT phosphorylation and interaction with GRB2, and also promoted the endocytosis of LAT.
[Proceedings of the National Academy of Sciences of the United States of America]
Liu, C., Xu, X., Han, L., Wan, X., Zheng, L., Li, C., Liao, Z., Xiao, J., Zhong, R., Zheng, X., Wang, Q., Li, Z., Chen, H., Wei, B., & Wang, H. (2020). LRCH1 deficiency enhances LAT signalosome formation and CD8+ T cell responses against tumors and pathogens. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2000970117 Cite
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Multiple Signaling Roles of CD3ε and Its Application in CAR-T Cell Therapy

Scientists found that incorporation of the CD3ε cytoplasmic domain into a second-generation chimeric antigen receptor (CAR) improved antitumor activity of CAR-T cells.
[Cell]
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IFN-γ Promoted Exosomes from Mesenchymal Stem Cells to Attenuate Colitis via miR-125a and miR-125b

Exosomes were isolated from control and IFN-γ-primed mesenchymal stem cells and were verified by transmission electron microscope and immunofluorescence staining.
[Cell Death & Disease]
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Induced Pluripotent Stem Cell-Derived Natural Killer Cells Gene-Modified to Express Chimeric Antigen Receptor-Targeting Solid Tumors

Scientists describe the characteristics of natural killer (NK) cells from multiple cell sources, including PSCs, the chimeric antigen receptor (CAR)-modification method and strategy for these NK cells.
[International Journal of Hematology]
Ueda, T., & Kaneko, S. (2020). Induced pluripotent stem cell-derived natural killer cells gene-modified to express chimeric antigen receptor-targeting solid tumors. International Journal of Hematology. https://doi.org/10.1007/s12185-020-02951-5 Cite
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