Zentalis Pharmaceuticals Announces the Initiation of Multiple Early-Stage Clinical Trials

Zentalis Pharmaceuticals, Inc. announced that the company has initiated patient dosing in three new combination and monotherapy clinical trials.
[Zentalis Pharmaceuticals, Inc.]
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Combination of Anti-PD-1 Antibody with P-GEMOX as a Potentially Effective Immunochemotherapy for Advanced Natural Killer/T Cell Lymphoma

Scientists report the efficacy of anti-programmed death 1 antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced natural killer/T cell lymphoma.
[Signal Transduction and Targeted Therapy]
Cai, J., Liu, P., Huang, H., Li, Y., Ma, S., Zhou, H., Tian, X., Zhang, Y., Gao, Y., Xia, Y., Zhang, X., Yang, H., Li, L., & Cai, Q. (2020). Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma. Signal Transduction and Targeted Therapy, 5(1), 1–9. https://doi.org/10.1038/s41392-020-00331-3 Cite
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Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4

Investigators showed that positive coactivator 4 (PC4) orchestrated chromatin structure and gene expression in mature B cells. B-cell-specific PC4-deficient mice showed impaired production of antibody upon antigen stimulation.
[Cell Reports]
Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4: Cell Reports. (n.d.). Retrieved January 5, 2021, from https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31506-0 Cite
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Targeting eIF4F Translation Initiation Complex with SBI-756 Sensitises B Lymphoma Cells to Venetoclax

Investigators tested inhibitors of cap-dependent mRNA translation for the ability to sensitise diffuse large B-cell lymphoma and mantle cell lymphoma cells to apoptosis by venetoclax.
[British Journal of Cancer]
Herzog, L., Walters, B., Buono, R., Lee, J. S., Mallya, S., Fung, A., Chiu, H., Nguyen, N., Li, B., Pinkerton, A. B., Jackson, M. R., Schneider, R. J., Ronai, Z. A., & Fruman, D. A. (2020). Targeting eIF4F translation initiation complex with SBI-756 sensitises B lymphoma cells to venetoclax. British Journal of Cancer, 1–12. https://doi.org/10.1038/s41416-020-01205-9 Cite
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Heterogeneity of Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma

Functional characterization of intratumoral Tregs was performed by a proliferation assay using FACS-sorted Tregs as suppressor cells and autologous CellTrace Violet-labelled T effector cells as responder cells.
[Blood]
Spasevska, I., Josefsson, S., Blaker, Y. N., Steen, C. B., Sharma, A., Kushekhar, K., Meyer, S., Kolstad, A., Beiske, K., Holte, H., Østenstad, B., Kimby, E., Olweus, J., Tasken, K., Lorenz, S., Smeland, E. B., Alizadeh, A. A., Huse, K., & Myklebust, J. H. (2020). Heterogeneity of Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma. Blood, 136(Supplement 1), 27–28. https://doi.org/10.1182/blood-2020-142380 Cite
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Regulation of PD-L1 Expression Is a Novel Facet of Cyclic-AMP-Mediated Immunosuppression

Using normal and malignant lymphocytes from humans, and the phosphodiesterase 4b knockout mouse, scientists found that cAMP induced PD-L1 transcription and protein expression.
[Leukemia]
Sasi, B., Ethiraj, P., Myers, J., Lin, A.-P., Jiang, S., Qiu, Z., Holder, K. N., & Aguiar, R. C. T. (2020). Regulation of PD-L1 expression is a novel facet of cyclic-AMP-mediated immunosuppression. Leukemia, 1–12. https://doi.org/10.1038/s41375-020-01105-0 Cite
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Indication and Benefit of Upfront Hematopoietic Stem Cell Transplantation for T-Cell Lymphoblastic Lymphoma in the Era of ALL-Type Induction Therapies

Investigators performed a multicenter retrospective cohort study of patients with T-cell lymphoblastic lymphoma treated using leukemia-type initial therapies to compare the outcomes after hematopoietic stem cell transplantation at different disease stages.
[Scientific Reports]
Morita-Fujita, M., Arai, Y., Yoshioka, S., Ishikawa, T., Kanda, J., Kondo, T., Akasaka, T., Ueda, Y., Imada, K., Moriguchi, T., Yago, K., Kitano, T., Yonezawa, A., Nohgawa, M., & Takaori-Kondo, A. (2020). Indication and benefit of upfront hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma in the era of ALL-type induction therapies. Scientific Reports, 10(1), 21418. https://doi.org/10.1038/s41598-020-78334-x Cite
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Fate Therapeutics Reports Positive Interim Data from its Phase I Study of FT516 in Combination with Rituximab for B-Cell Lymphoma

Fate Therapeutics, Inc. announced positive interim data from the Company’s dose escalation Phase I study of FT516 in combination with rituximab for patients with relapsed/refractory B-cell lymphoma.
[Fate Therapeutics, Inc.]
Press Release
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Stem Cell Characteristics Promote Aggressiveness of Diffuse Large B-Cell Lymphoma

Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model.
[Scientific Reports]
Chang, K.-C., Chen, R.-Y., Wang, Y.-C., Hung, L.-Y., Medeiros, L. J., Chen, Y.-P., Chen, T.-Y., Yang, J.-C., & Chiang, P.-M. (2020). Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma. Scientific Reports, 10(1), 21342. https://doi.org/10.1038/s41598-020-78508-7 Cite
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Genetic and Epigenetic Determinants of Diffuse Large B-Cell Lymphoma

One of the major insights produced by such research is that diffuse large B-cell lymphoma (DLBCL) almost always stems from genetic damage that occurs during the germinal center reaction, which is required for the production of high-affinity antibodies.
[Blood Cancer Journal]
Bakhshi, T. J., & Georgel, P. T. (2020). Genetic and epigenetic determinants of diffuse large B-cell lymphoma. Blood Cancer Journal, 10(12), 1–23. https://doi.org/10.1038/s41408-020-00389-w Cite
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Genome-Wide Screens Identify Lineage- and Tumor-Specific Genes Modulating MHC-I- and MHC-II-Restricted Immunosurveillance of Human Lymphomas

To identify the global regulatory networks controlling antigen presentation, scientists employed genome-wide screening in human diffuse large B cell lymphomas.
[Immunity]
Dersh, D., Phelan, J. D., Gumina, M. E., Wang, B., Arbuckle, J. H., Holly, J., Kishton, R. J., Markowitz, T. E., Seedhom, M. O., Fridlyand, N., Wright, G. W., Huang, D. W., Ceribelli, M., Thomas, C. J., Lack, J. B., Restifo, N. P., Kristie, T. M., Staudt, L. M., & Yewdell, J. W. (2020). Genome-wide Screens Identify Lineage- and Tumor-Specific Genes Modulating MHC-I- and MHC-II-Restricted Immunosurveillance of Human Lymphomas. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.11.002 Cite
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