Agilent - Breakthroughs in Immunotherapy- 2019 - 14

Breakthroughs in Immunotherapy

elicit an aerobic program consistent with central memory formation
and persistence. In contrast, engineering with the CD28 coreceptor
signaling domain reprograms metabolism towards aerobic
glycolysis resulting in enhanced effector memory cell fate. This
study was a powerful proof of concept for engineering metabolic
traits to establish the right balance of effector and memory cells to
address immune cell exhaustion and persistence in hostile tumor
microenvironments paving the way for durable memory and
immunosurveillance. n
References
1. FDA (2017) FDA approval brings first gene therapy to the United States,
[News Release], 30 August 30.
2. FDA (2017) FDA approves CAR-T cell therapy to treat adults with certain types of
large B-cell lymphoma, [News Release], 18 October.
3. M.A. Morgan et al. Engineering CAR-T Cells for Improved Function Against Solid
Tumors. Frontiers in Immunology, 9: article 2493 (2018)
4. D.J. Dellinger et al. Streamlined Process for the Chemical Synthesis of RNA
Using 2′-O-Thionocarbamate-Protected Nucleoside Phosphoramidites in the
Solid Phase. Journal of the American Chemical Society, 133(30):11540-11556
(2011)
5. A. Hendel et al. Chemically modified guide RNAs enhance CRISPR-Cas genome
editing in human primary cells. Nature Biotechnology, 33(9):985-989 (2015)
6. D.E. Ryan et al. Improving CRISPR-Cas specificity with chemical modifications
in single-guide RNAs. Nucleic Acids Research, 46(2):792-803 (2018)
7. M. Hegde et al. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor
antigen escape. The Journal of Clinical Investigation, 126(8):3036-52 (2016)
8. O.U. Kawalekar et al. Distinct Signaling of Coreceptors Regulates Specific
Metabolism Pathways and Impacts Memory Development in CAR T Cells.
Immunity 44:380-390 (2016)

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Agilent - Breakthroughs in Immunotherapy- 2019

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