Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo

The authors created a chimeric antigen-receptor (CAR) that was capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation domain. Addition of a small molecule ligand triggered exposure of a cryptic degron within the ligand-induced degradation domain (LID), resulting in proteasomal degradation of the CAR-LID fusion protein and loss of CAR on the surface of T cells.
[Molecular Therapy]
Ligand-induced degradation of a CAR permits reversible remote control of CAR T cell activity in vitro and in vivo: Molecular Therapy. (n.d.). Retrieved June 16, 2020, from https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30294-X Cite
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CRISPR-Cas9 Mediated Glucocorticoid Resistance in Virus-Specific T Cells for Adoptive T-Cell Therapy Post Transplantation

In order to deliver protection against viral pathogens and allow at the same time necessary steroid therapy, scientists generated glucocorticoid-resistant T cells by CRISPR/Cas9-mediated knockout of the glucocorticoid receptor in primary human virus-specific T-cell products.
[Molecular Therapy]
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Novel Long Non-Coding RNA lncAMPC Promotes Metastasis and Immunosuppression in Prostate Cancer by Stimulating LIF/LIFR Expression

The biological capacity of lncRNA named lncRNA activated in metastatic PCa (lncAMPC) in prostate cancer (PCa) was demonstrated both in vitro and in vivo. The lncAMPC was overexpressed in tumor tissue and urine of metastatic PCa patients and promoted PCa tumorigenesis and metastasis.
[Molecular Therapy]
Zhang, W., Shi, X., Chen, R., Zhu, Y., Peng, S., Chang, Y., … Ren, S. (2020). Novel long non-coding RNA lncAMPC promotes metastasis and immunosuppression in prostate cancer by stimulating LIF/LIFR expression. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2020.06.013 Cite
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Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch

Researchers showed that circulating tumor cells isolated from immunotherapy-resistant metastatic melanoma patients expressed higher levels of nuclear lysine specific demethylase 1 (LSD1) phosphorylated at serine 111 compared to responders, which is associated with co-expression of stem-like, mesenchymal genes.
[Frontiers in Immunology]
Tu, W. J., McCuaig, R. D., Tan, A. H. Y., Hardy, K., Seddiki, N., Ali, S., … Rao, S. (2020). Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.01228 Cite
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Tumor-Associated Macrophages in Classical Hodgkin Lymphoma: Hormetic Relationship to Outcome

MYC+ cells accounted for 21% and 18% of CD68+ and CD163+ cells, respectively. Numbers of MYC macrophages were significantly higher in EBV+ cases while no differences were observed for MYC+ macrophages between EBV+ and EBV cases.
[Scientific Reports]
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Reference Genes for Expression Studies in Human CD8+ Naïve and Effector Memory T Cells under Resting and Activating Conditions

Researchers evaluated twelve commonly used reference gene products in human naïve and effector memory CD8+ T cells under non-activated and activated conditions. They used five different statistical approaches for data analysis.
[Scientific Reports]
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convertibleCARs: A Chimeric Antigen Receptor System for Flexible Control of Activity and Antigen Targeting

An inert form of the human NKG2D extracellular domain (iNKG2D) was engineered as the ectodomain of the chimeric antigen receptor (CAR) to generate convertibleCARTM-T cells. These cells were specifically directed to kill antigen-expressing target cells only in the presence of an activating bispecific adapter comprised of an iNKG2D-exclusive ULBP2-based ligand fused to an antigen-targeting antibody
[Communications Biology]
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The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway

Investigators summarize and question what is known and remains to be discovered about the TREM2 signaling pathway, track the consequences of its activation in physiological niches and pathological contexts, and highlight the promising potential of therapeutic manipulation of TREM2 signaling.
[Cell]
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DNA of Neutrophil Extracellular Traps Promotes Cancer Metastasis via CCDC25

Investigators showed that neutrophil extracellular traps (NETs) were abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs could predict the occurrence of liver metastases in patients with early-stage breast cancer.
[Nature]
Yang, L., Liu, Q., Zhang, X., Liu, X., Zhou, B., Chen, J., … Song, E. (2020). DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature, 1–6. https://doi.org/10.1038/s41586-020-2394-6 Cite
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Old Dogs, New Trick: Classic Cancer Therapies Activate cGAS

The authors review the antitumor roles of the GMP-AMP synthase (cGAS-STING) pathway during tumorigenesis, cancer immune surveillance, and cancer therapies. They also highlight classic cancer therapies that elicit antitumor immune responses through cGAS activation.
[Cell Research]
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Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-Tumor Activity

The authors developed human cytokine-inducible SH2-containing protein-knockout (CISH−/−) NK cells using an induced pluripotent stem cell-derived NK cell (iPSC-NK cell) platform. CISH−/− iPSC-NK cells demonstrated increased IL-15-mediated JAK-STAT signaling activity.
[Cell Stem Cell]
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