Cancer Therapy Search Gets Boost from NIH Grant

The National Institutes of Health (NIH) awarded Lydia Kavraki, PhD, of Rice University’s Brown School of Engineering, a U01 grant to develop a new approach to model and analyze protein-ligand interactions in cancer research. The end goal is to create a proteomics toolkit, PROTEAN-CR, focused on the structural analysis of protein-ligand interactions.
[Genetic Engineering & Biotechnology News]
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Could This Be the ‘Holy Grail for Cell Therapy’?

Notch Therapeutics is a Canadian company with a potential breakthrough in the form of a cost-effective and reliable manufacturing platform called Engineered Thymic Niche. The technology can create universally compatible T-cells from donor stem cells on an industrial scale, offering an efficient way to mass manufacture T-cell therapies that are of consistent quality.
[Notch Therapeutics]
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IN8bio Completes Treatment of First Cohort in Phase I Clinical Trial with Gamma Delta T-Cell Therapy in Patients with Newly Diagnosed Glioblastoma Multiforme

IN8bio, Inc. announced an update from the ongoing Phase I clinical trial of INB-200, its DeltEx drug resistant immunotherapy , MGMT-gene modified gamma delta T-cells in patients with newly diagnosed GBM.
[IN8bio, Inc.]
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Tumor Microenvironmental Cytokines Bound to Cancer Exosomes Determine Uptake by Cytokine Receptor-Expressing Cells and Biodistribution

Researchers showed that microenvironmental cytokines, particularly CCL2, decorated cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs.
[Nature Communications]
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FOXA1 Overexpression Suppresses Interferon Signaling and Immune Response in Cancer

Scientists found that FOXA1 overexpression inversely correlated with interferon signature and antigen presentation gene expression in prostate cancer and breast cancer patients.
[Journal of Clinical Investigation]
He, Y., Wang, L., Wei, T., Xiao, Y.-T., Sheng, H., Su, H., Hollern, D. P., Zhang, X., Ma, J., Wen, S., Xie, H., Yan, Y., Pan, Y., Hou, X., Tang, X., Suman, V. J., Carter, J. M., Weinshilboum, R., Wang, L., … Huang, H. (2021). FOXA1 overexpression suppresses interferon signaling and immune response in cancer. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI147025 Cite
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Human Immune System Adaptations to Simulated Microgravity Revealed by Single-Cell Mass Cytometry

Researchers employed a high-dimensional mass cytometry approach to characterize over 250 cell-specific functional responses in 18 innate and adaptive immune cell subsets exposed to 1G or simulated µG using the Rotating Wall Vessel.
[Scientific Reports]
Spatz, J. M., Fulford, M. H., Tsai, A., Gaudilliere, D., Hedou, J., Ganio, E., Angst, M., Aghaeepour, N., & Gaudilliere, B. (2021). Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry. Scientific Reports, 11(1), 11872. https://doi.org/10.1038/s41598-021-90458-2 Cite
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GATA3 Induces Mitochondrial Biogenesis in Primary Human CD4+ T Cells during DNA Damage

Investigators showed a mechanism utilised by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK.
[Nature Communications]
Callender, L. A., Schroth, J., Carroll, E. C., Garrod-Ketchley, C., Romano, L. E. L., Hendy, E., Kelly, A., Lavender, P., Akbar, A. N., Chapple, J. P., & Henson, S. M. (2021). GATA3 induces mitochondrial biogenesis in primary human CD4+ T cells during DNA damage. Nature Communications, 12(1), 3379. https://doi.org/10.1038/s41467-021-23715-7 Cite
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Genetic Variation Associated with Thyroid Autoimmunity Shapes the Systemic Immune Response to PD-1 Checkpoint Blockade

The authors studied endocrine immune related adverse events from seven clinical trials across six cancers where atezolizumab was combined with chemotherapies and compared to standard of care.
[Nature Communications]
Khan, Z., Hammer, C., Carroll, J., Di Nucci, F., Acosta, S. L., Maiya, V., Bhangale, T., Hunkapiller, J., Mellman, I., Albert, M. L., McCarthy, M. I., & Chandler, G. S. (2021). Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade. Nature Communications, 12(1), 3355. https://doi.org/10.1038/s41467-021-23661-4 Cite
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MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING

Scientists examined 81 lung cancer patients under immune checkpoint blockade (ICB) treatment and found that patients with MET amplification were resistant to ICB and had a poor progress-free survival.
[Cancer Discovery]
Zhang, Y., Yang, Q., Zeng, X., Wang, M., Dong, S., Yang, B., Tu, X., Wei, T., Xie, W., Zhang, C., Guo, Q., Kloeber, J. A., Cao, Y., Guo, G., Zhou, Q., Zhao, F., Huang, J., Liu, L., Zhang, K., … Lou, Z. (2021). MET amplification attenuates lung tumor response to immunotherapy by inhibiting STING. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-1500 Cite
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Interleukins in Cancer: From Biology to Therapy

Interleukins can nurture an environment enabling and favouring cancer growth while simultaneously being essential for a productive tumour-directed immune response. These properties of interleukins can be exploited to improve immunotherapies to promote effectiveness as well as to limit side effects.
[Nature Reviews Cancer]
Briukhovetska, D., Dörr, J., Endres, S., Libby, P., Dinarello, C. A., & Kobold, S. (2021). Interleukins in cancer: from biology to therapy. Nature Reviews Cancer, 1–19. https://doi.org/10.1038/s41568-021-00363-z Cite
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Ex Vivo Immune Profiling in Patient Blood Enables Quantification of Innate Immune Effector Functions

Lab-based immune profiling often relies solely on quantification of cell numbers, researchers used an ex vivo whole-blood infection model in combination with biomathematical modeling to quantify functional parameters of innate immune cells in blood from patients undergoing cardiac surgery.
[Scientific Reports]
Lehnert, T., Leonhardt, I., Timme, S., Thomas-Rüddel, D., Bloos, F., Sponholz, C., Kurzai, O., Figge, M. T., & Hünniger, K. (2021). Ex vivo immune profiling in patient blood enables quantification of innate immune effector functions. Scientific Reports, 11(1), 12039. https://doi.org/10.1038/s41598-021-91362-5 Cite
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