Genetic Engineering of T Cells for Immunotherapy

Scientists review the principles by which our knowledge of genetics and genome engineering will drive the next generation of adoptive T cell therapies.
[Nature Reviews Genetics]
Ellis, G. I., Sheppard, N. C., & Riley, J. L. (2021). Genetic engineering of T cells for immunotherapy. Nature Reviews Genetics, 1–21. https://doi.org/10.1038/s41576-021-00329-9 Cite
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Epcoritamab Induces Potent Anti-Tumor Activity against Malignant B-Cells from Patients with DLBCL, FL and MCL, Irrespective of Prior CD20 Monoclonal Antibody Treatment

Researchers assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed and relapsed/refractory B-cell non-Hodgkin lymphoma patients.
[Blood Cancer Journal]
van der Horst, H. J., de Jonge, A. V., Hiemstra, I. H., Gelderloos, A. T., Berry, D. R. A. I., Hijmering, N. J., van Essen, H. F., de Jong, D., Chamuleau, M. E. D., Zweegman, S., Breij, E. C. W., Roemer, M. G. M., & Mutis, T. (2021). Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. Blood Cancer Journal, 11(2), 1–8. https://doi.org/10.1038/s41408-021-00430-6 Cite
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Affinity-Coupled CCL22 Promotes Positive Selection in Germinal Centres

Scientists showed that, upon stimulation of CD40, germinal centre B cells upregulated the chemokine CCL22 and to a lesser extent CCL17.
[Nature]
Adam, A., Fontes-Garfias, C. R., Sarathy, V. V., Liu, Y., Luo, H., Davis, E., Li, W., Muruato, A. E., Wang, B., Ahatov, R., Mahmoud, Y., Shan, C., Osman, S. R., Widen, S. G., Barrett, A. D. T., Shi, P.-Y., & Wang, T. (2021). A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission. Npj Vaccines, 6(1), 1–11. https://doi.org/10.1038/s41541-021-00288-6 Cite
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Notch2-Mediated Plasticity between Marginal Zone and Follicular B Cells

Investigators showed induced Notch2IC-expression in follicular B (FoB) cells re-programs mature FoB cells into bona fide marginal zone B cells as was evident from the surface phenotype, localization, immunological function and transcriptome of these cells.
[Nature Communications]
Lechner, M., Engleitner, T., Babushku, T., Schmidt-Supprian, M., Rad, R., Strobl, L. J., & Zimber-Strobl, U. (2021). Notch2-mediated plasticity between marginal zone and follicular B cells. Nature Communications, 12(1), 1111. https://doi.org/10.1038/s41467-021-21359-1 Cite
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A Genetically Stable Zika Virus Vaccine Candidate Protects Mice against Virus Infection and Vertical Transmission

The authors generated a Zika virus mutant, ZE4B-36, which combined mutations in both E glycosylation and NS4B P36.
[npj Vaccines]
Adam, A., Fontes-Garfias, C. R., Sarathy, V. V., Liu, Y., Luo, H., Davis, E., Li, W., Muruato, A. E., Wang, B., Ahatov, R., Mahmoud, Y., Shan, C., Osman, S. R., Widen, S. G., Barrett, A. D. T., Shi, P.-Y., & Wang, T. (2021). A genetically stable Zika virus vaccine candidate protects mice against virus infection and vertical transmission. Npj Vaccines, 6(1), 1–11. https://doi.org/10.1038/s41541-021-00288-6 Cite
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Single-Cell Analysis of Human B Cell Maturation Predicts How Antibody Class Switching Shapes Selection Dynamics

Scientists provide a comprehensive roadmap of human B cell maturation with single-cell transcriptomics matched with bulk and single-cell antibody repertoires to define gene expression, antibody repertoires, and clonal sharing of B cell states at single-cell resolution.
[Science Immunology]
King, H. W., Orban, N., Riches, J. C., Clear, A. J., Warnes, G., Teichmann, S. A., & James, L. K. (2021). Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics. Science Immunology, 6(56). https://doi.org/10.1126/sciimmunol.abe6291 Cite
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Mesenchymal Stromal Cells Attenuate Post-Stroke Infection by Preventing Caspase-1-Dependent Splenic Marginal Zone B Cell Death

Scientists showed that intravenously administered MSCs preferentially migrate to the marginal zone (MZ) of the spleen, preserving injured MZ B cells and ameliorating post-stroke infection and mortality in the mouse middle cerebral artery occlusion model of acute ischemic stroke.
[Signal Transduction and Targeted Therapy]
Huang, Y., Wang, J., Lai, X., Qiu, Y., Cai, J., Ma, Y., Liu, Y., Qiu, W., Lu, Z., & Xiang, A. P. (2021). Mesenchymal stromal cells attenuate post-stroke infection by preventing caspase-1-dependent splenic marginal zone B cell death. Signal Transduction and Targeted Therapy, 6(1), 1–3. https://doi.org/10.1038/s41392-020-00415-0 Cite
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RUNX2 Regulates Leukemic Cell Metabolism and Chemotaxis in High-Risk T Cell Acute Lymphoblastic Leukemia

The authors report direct transcriptional regulation of CXCR4 signaling by RUNX2, thereby promoting chemotaxis, adhesion and homing to medullary and extramedullary sites.
[Journal of Clinical Investigation]
Matthijssens, F., Sharma, N. D., Nysus, M., Nickl, C. K., Kang, H., Perez, D. R., Lintermans, B., Loocke, W. V., Roels, J., Peirs, S., Demoen, L., Pieters, T., Reunes, L., Lammens, T., Moerloose, B. D., Nieuwerburgh, F. V., Deforce, D. L., Cheung, L. C., Kotecha, R. S., … Matlawska-Wasowska, K. (2021). RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI141566 Cite
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Alterations of 5-Hydroxymethylation in Circulating Cell-Free DNA Reflect Molecular Distinctions of Subtypes of Non-Hodgkin Lymphoma

Scientists profiled genome-wide 5-methylcytosines in circulating cell-free DNA from 73 newly diagnosed patients with diffuse large B-cell lymphoma and follicular lymphoma
[npj Genomic Medicine]
Chiu, B. C.-H., Chen, C., You, Q., Chiu, R., Venkataraman, G., Zeng, C., Zhang, Z., Cui, X., Smith, S. M., He, C., & Zhang, W. (2021). Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma. Npj Genomic Medicine, 6(1), 1–10. https://doi.org/10.1038/s41525-021-00179-8 Cite
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Atypical B Cells Are Part of an Alternative Lineage of B Cells That Participates in Responses to Vaccination and Infection in Humans

Researchers used single-cell RNA sequencing to examine the diversity of both antigen-specific and total B cells in healthy subjects and malaria-exposed individuals.
[Cell Reports]
Sutton, H. J., Aye, R., Idris, A. H., Vistein, R., Nduati, E., Kai, O., Mwacharo, J., Li, X., Gao, X., Andrews, T. D., Koutsakos, M., Nguyen, T. H. O., Nekrasov, M., Milburn, P., Eltahla, A., Berry, A. A., Kc, N., Chakravarty, S., Sim, B. K. L., … Cockburn, I. A. (2021). Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans. Cell Reports, 34(6). https://doi.org/10.1016/j.celrep.2020.108684 Cite
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mRNA Vaccine-Elicited Antibodies to SARS-CoV-2 and Circulating Variants

Scientists report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna or Pfizer-BioNTech vaccines.
[Nature]
Wang, Z., Schmidt, F., Weisblum, Y., Muecksch, F., Barnes, C. O., Finkin, S., Schaefer-Babajew, D., Cipolla, M., Gaebler, C., Lieberman, J. A., Oliveira, T. Y., Yang, Z., Abernathy, M. E., Huey-Tubman, K. E., Hurley, A., Turroja, M., West, K. A., Gordon, K., Millard, K. G., … Nussenzweig, M. C. (2021). mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature, 1–10. https://doi.org/10.1038/s41586-021-03324-6 Cite
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