Engineered AAV8 Capsid Acquires Heparin and AVB Sepharose Binding Capacity but Has Altered In Vivo Transduction Efficiency

In vivo comparison by intramuscular, intravenous, and intraperitoneal vector administration demonstrated a significant decrease in adeno-associated virus 8-AVB-heparan sulfate transduction efficiency without alteration of the transduction profile.
[Gene Therapy]
van Lieshout, L. P., Stegelmeier, A. A., Rindler, T. N., Lawder, J. J., Sorensen, D. L., Frost, K. L., Booth, S. A., Bridges, J. P., & Wootton, S. K. (2020). Engineered AAV8 capsid acquires heparin and AVB sepharose binding capacity but has altered in vivo transduction efficiency. Gene Therapy, 1–9. https://doi.org/10.1038/s41434-020-00198-7 Cite
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In Vivo CRISPR/Cas9 Targeting of Fusion Oncogenes for Selective Elimination of Cancer Cells

Scientists devised a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the fusion oncogene specifically in cancer cells.
[Nature Communications]
Martinez-Lage, M., Torres-Ruiz, R., Puig-Serra, P., Moreno-Gaona, P., Martin, M. C., Moya, F. J., Quintana-Bustamante, O., Garcia-Silva, S., Carcaboso, A. M., Petazzi, P., Bueno, C., Mora, J., Peinado, H., Segovia, J. C., Menendez, P., & Rodriguez-Perales, S. (2020). In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Nature Communications, 11(1), 5060. https://doi.org/10.1038/s41467-020-18875-x Cite
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Melphalan and Exportin 1 Inhibitors Exert Synergistic Anti-Tumor Effects in Preclinical Models of Human Multiple Myeloma

Multiple myeloma (MM) cells from newly diagnosed and relapsed/refractory MM patients were also sensitized by XPO1i to melphalan. In NOD/SCID-γ mice challenged with either parental 8226 or U266 MM and melphalan-resistant MM tumors, XPO1i/melphalan combination treatments demonstrated stronger synergistic anti-tumor effects than single-agent melphalan with minimal toxicity.
[Cancer Research]
Turner, J. G., Cui, Y., Bauer, A. A., Dawson, J. L., Gomez, J. A., Kim, J., Cubitt, C. L., Nishihori, T., Dalton, W. S., & Sullivan, D. M. (2020). Melphalan and exportin 1 inhibitors exert synergistic anti-tumor effects in preclinical models of human multiple myeloma. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-19-0677 Cite
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CD19-Specific CAR-T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor is Effective in Patients with PD-L1 Positive B-Cell Lymphoma

Scientists generated a novel anti-CD19 CAR expressing PD-1/CD28 chimeric switch-receptor. They then conducted a Phase Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1+ B-cell lymphoma.
[Clinical Cancer Research]
Liu, H., Lei, W., Zhang, C., Yang, C., Wei, J., Guo, Q., Guo, X., Chen, Z., Lu, Y., Young, K. H., Lu, Z., & Qian, W. (2020). CD19-Specific CAR-T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor is Effective in Patients with PD-L1 Positive B-Cell Lymphoma. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-1457 Cite
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Affimed Announces Dosing of First Patient in Phase I Clinical Trial of Cord Blood-Derived Natural Killer Cells in Combination with the Innate Cell Engager AFM13

Affimed N.V. announced that the first patient was successfully dosed with allogeneic cord blood-derived natural killer cells preloaded with AFM13 and has moved on to the AFM13 monotherapy phase of the treatment cycle. This therapy was developed through a research collaboration with The University of Texas MD Anderson Cancer Center.
[Affimed N.V.]
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In Vivo CRISPR/Cas9 Targeting of Fusion Oncogenes for Selective Elimination of Cancer Cells

Researchers devised a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the fusion oncogenes specifically in cancer cells.
[Nature Communications]
Martinez-Lage, M., Torres-Ruiz, R., Puig-Serra, P., Moreno-Gaona, P., Martin, M. C., Moya, F. J., Quintana-Bustamante, O., Garcia-Silva, S., Carcaboso, A. M., Petazzi, P., Bueno, C., Mora, J., Peinado, H., Segovia, J. C., Menendez, P., & Rodriguez-Perales, S. (2020). In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Nature Communications, 11(1), 5060. https://doi.org/10.1038/s41467-020-18875-x Cite
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LncRNA-AK149641 Regulates the Secretion of Tumor Necrosis Factor-α in P815 Mast Cells by Targeting the Nuclear Factor-Kappa B Signaling Pathway

Scientists elucidated the function and possible role of a novel lncRNA, called lncRNA-AK149641, in the mechanism of lipopolysaccharide-induced inflammatory response in P815 mast cells.
[Scientific Reports]
Zhou, Y., Gu, L., Zhang, J., Pan, J., Zhang, J., Zhao, D., & Liu, F. (2020). LncRNA-AK149641 regulates the secretion of tumor necrosis factor-α in P815 mast cells by targeting the nuclear factor-kappa B signaling pathway. Scientific Reports, 10(1), 16655. https://doi.org/10.1038/s41598-020-73186-x Cite
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In Vivo Imaging of Long-Term Accumulation of Cancer-Derived Exosomes using a BRET-Based Reporter

Transplantation of CD63-Antares2-expressing prostate cancer cells into mice allowed determining the amount of cancer-derived exosomes released from primary tumors into the bloodstream and visualizing the long-term homing behavior of exosomes to their target organs or tissues.
[Scientific Reports]
Hikita, T., Miyata, M., Watanabe, R., & Oneyama, C. (2020). In vivo imaging of long-term accumulation of cancer-derived exosomes using a BRET-based reporter. Scientific Reports, 10(1), 16616. https://doi.org/10.1038/s41598-020-73580-5 Cite
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bluebird bio Announces European Medicines Agency’s Acceptance of Marketing Authorization Application (MAA) for elivaldogene autotemcel (eli-cel, Lenti-D™) Gene Therapy for Cerebral Adrenoleukodystrophy (CALD)

bluebird bio, Inc. announced that the European Medicines Agency accepted the company’s MAA for its investigational elivaldogene autotemcel gene therapy for the treatment of patients with CALD.
[bluebird bio, Inc.]
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Therapeutic Angiogenesis Using Autologous Adipose-Derived Regenerative Cells in Patients with Critical Limb Ischaemia in Japan: A Clinical Pilot Study

Adipose tissue was obtained by ordinary liposuction method. Isolated ADRCs were injected into the ischaemic limb. Scientists performed TACT-ADRC procedure in five patients with CLI.
[Scientific Reports]
Therapeutic angiogenesis using autologous adipose-derived regenerative cells in patients with critical limb ischaemia in Japan: a clinical pilot study | Scientific Reports. (n.d.). Retrieved October 5, 2020, from https://www.nature.com/articles/s41598-020-73096-y Cite
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Itacitinib (INCB039110), a JAK1 inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-Cell Therapy

Researchers studied the effect of blocking JAK pathway signaling on CAR T-cell proliferation, anti-tumor activity and cytokine levels in in vitro and in vivo models. They report that itacitinib, a potent, selective JAK1 inhibitor, was able to significantly and dose-dependently reduce levels of multiple cytokines implicated in CRS in several in vitro and in vivo models.
[Clinical Cancer Research]
Itacitinib (INCB039110), a JAK1 inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-Cell Therapy | Clinical Cancer Research. (n.d.). Retrieved October 5, 2020, from https://clincancerres.aacrjournals.org/content/early/2020/09/30/1078-0432.CCR-20-1739 Cite
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