Bacterial Outer Membrane Vesicles Presenting Programmed Death 1 for Improved Cancer Immunotherapy via Immune Activation and Checkpoint Inhibition

Investigators report the development of genetically engineered outer membrane vesicles whose surface has been modified by insertion of the ectodomain of programmed death 1.
[ACS Nano]
Li, Y., Zhao, R., Cheng, K., Zhang, K., Wang, Y., Zhang, Y., Li, Y., Liu, G., Xu, J., Xu, J., Anderson, G. J., Shi, J., Ren, L., Zhao, X., & Nie, G. (2020). Bacterial Outer Membrane Vesicles Presenting Programmed Death 1 for Improved Cancer Immunotherapy via Immune Activation and Checkpoint Inhibition. ACS Nano. https://doi.org/10.1021/acsnano.0c03776 Cite
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Adaptive T-Cell Immunity Controls Senescence-Prone MyD88- or CARD11-Mutant B-Cell Lymphomas

Scientists functionally investigate primary mouse lymphomas that formed in recipient mice of Eµ-myc transgenic hematopoietic stem cells stably transduced with naturally occurring NF-kB mutants.
[Blood]
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Immunobiology and Immunotherapy of HCC: Spotlight on Innate and Innate-Like Immune Cells

Investigators summarize and highlight the role of these cells in liver cancer and propose strategies to therapeutically target them. They also discuss current immunotherapeutic strategies in hepatocellular carcinoma and outline recent advances in our understanding of how the therapeutic potential of these agents might be enhanced.
[Cellular & Molecular Immunology]
Ruf, B., Heinrich, B., & Greten, T. F. (2020). Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells. Cellular & Molecular Immunology, 1–16. https://doi.org/10.1038/s41423-020-00572-w Cite
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CD28 Co-Stimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-Cell Function

In vivo, researchers found that mice given CAR T cells with only a PYAP CD28 endodomain had a significant survival advantage, with 100% of mice alive after 62 days compared to 50% for mice with an unmutated endodomain.
[Cancer Immunology Research]
Boucher, J. C., Li, G., Kotani, H., Cabral, M. L., Morrissey, D., Lee, S. B., Spitler, K., Beatty, N. J., Cervantes, E. V., Shrestha, B., Yu, B., Kazi, A., Wang, X., Sebti, S. M., & Davila, M. L. (2020). CD28 co-stimulatory domain-targeted mutations enhance chimeric antigen receptor T-cell function. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0253 Cite
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FDA Approves Merck’s KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy for Patients with Locally Recurrent Unresectable or Metastatic Triple‑Negative Breast Cancer Whose Tumors Express PD-L1 (CPS ≥10)

Merck announced that the US FDA approved KEYTRUDA®, Merck’s anti-PD-1 therapy, in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC. The approval was based on results from the Phase III KEYNOTE-355 trial, where KEYTRUDA® in combination with chemotherapy – paclitaxel, paclitaxel protein-bound or gemcitabine and carboplatin – significantly reduced the risk of disease progression or death by 35%.
[Merck & Co., Inc]
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Surface Oncology Announces FDA Fast Track Designation Granted by US Food and Drug Administration for SRF388 to Treat Liver Cancer

Surface Oncology develop next-generation immunotherapies that target the tumor microenvironment. They have announced that the US FDA has granted Fast Track designation to SRF388 for the treatment of patients with hepatocellular carcinoma, or liver cancer, who have been previously treated with standard therapies, such as vascular endothelial growth factor targeted agents and programmed death-ligand blockade.
[Surface Oncology]
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Merck Announces KEYNOTE-598 Trial Evaluating KEYTRUDA® (Pembrolizumab) in Combination with Ipilimumab versus KEYTRUDA Monotherapy in Certain Patients With Metastatic Non-Small Cell Lung Cancer to Stop for Futility and Patients to Discontinue Ipilimumab

Merck announced that it will be stopping KEYNOTE-598, a Phase III trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with ipilimumab, compared with KEYTRUDA monotherapy, for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1 with no EGFR or ALK genomic tumor aberrations.
[Merck & Co., Inc.]
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NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion

Scientists found nicotinamide phosphoribosyltransferase, the rate-limiting enzyme of the NAD + biogenesis, drives interferon γ-induced PD-L1 expression in multiple types of tumors and governs tumor immune evasion in a CD8 + T cell-dependent manner.
[Cell Metabolism]
Lv, H., Lv, G., Chen, C., Zong, Q., Jiang, G., Ye, D., Cui, X., He, Y., Xiang, W., Han, Q., Tang, L., Yang, W., & Wang, H. (2020). NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metabolism, 0(0). https://doi.org/10.1016/j.cmet.2020.10.021 Cite
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Platelet PD-L1 Suppresses Anti-Cancer Immune Cell Activity in PD-L1 Negative Tumors

Researchers showed that platelet-derived programmed cell death protein-1 (PD-L1) regulated the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promoted T cell-induced cancer cytotoxicity.
[Scientific Reports]
Zaslavsky, A. B., Adams, M. P., Cao, X., Maj, T., Choi, J. E., Stangl-Kremser, J., Patel, S., Putelo, A., Lee, S. K., Nallandhighal, S., Kasputis, A., Alva, A., Lew, M., Qin, A., Mehra, R., Morgan, T. M., Salami, S. S., Reichert, Z., Udager, A., … Palapattu, G. S. (2020). Platelet PD-L1 suppresses anti-cancer immune cell activity in PD-L1 negative tumors. Scientific Reports, 10(1), 19296. https://doi.org/10.1038/s41598-020-76351-4 Cite
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Inhibition of Glutamine Utilization Synergizes with Immune Checkpoint Inhibitor to Promote Antitumor Immunity

Scientists report that limiting glutamine metabolism in cancer cells bolstered the effectiveness of anti-programmed death ligand-1 antibody.
[Molecular Cell]
Byun, J.-K., Park, M., Lee, S., Yun, J. W., Lee, J., Kim, J. S., Cho, S. J., Jeon, H.-J., Lee, I.-K., Choi, Y.-K., & Park, K.-G. (2020). Inhibition of Glutamine Utilization Synergizes with Immune Checkpoint Inhibitor to Promote Antitumor Immunity. Molecular Cell, 0(0). https://doi.org/10.1016/j.molcel.2020.10.015 Cite
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iPSC-Derived NK Cells Maintain High Cytotoxicity and Enhance In Vivo Tumor Control in Concert with T Cells and Anti–PD-1 Therapy

Natural killer (NK) cells have the potential to augment checkpoint inhibition therapies, such as PD-L1/PD-1 blockade, because NK cells mediate both direct tumor lysis and T cell activation and recruitment.
[Science Translational Medicine]
Cichocki, F., Bjordahl, R., Gaidarova, S., Mahmood, S., Abujarour, R., Wang, H., Tuininga, K., Felices, M., Davis, Z. B., Bendzick, L., Clarke, R., Stokely, L., Rogers, P., Ge, M., Robinson, M., Rezner, B., Robbins, D. L., Lee, T. T., Kaufman, D. S., … Miller, J. S. (2020). iPSC-derived NK cells maintain high cytotoxicity and enhance in vivo tumor control in concert with T cells and anti–PD-1 therapy. Science Translational Medicine, 12(568). https://doi.org/10.1126/scitranslmed.aaz5618 Cite
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