Single-cell genomic approaches for developing the next generation of immunotherapies


Recent progress in single-cell genomics urges its application in drug development, particularly of cancer immunotherapies. Current immunotherapy pipelines are focused on functional outcome and simple cellular and molecular readouts. A thorough mechanistic understanding of the cells and pathways targeted by immunotherapy agents is lacking, which limits the success rate of clinical trials. A large leap forward can be made if the immunotherapy target cells and pathways are characterized at high resolution before and after treatment, in clinical cohorts and model systems. This will enable rapid development of effective immunotherapies and data-driven design of synergistic drug combinations. In this Perspective, we discuss how emerging single-cell genomic technologies can serve as an engine for target identification and drug development.

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Fig. 1: Challenges in understanding the cellular effects of immunotherapies.
Fig. 2: Single-cell analysis as an engine for driving drug development.
Fig. 3: Incorporation of single-cell genomics in clinical trials.


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We thank J.-P. Halle (Merck KGaA, Darmstadt) for critical discussions, input and feedback on this manuscript, and G. Brodsky from the Scientific Illustration unit of the Weizmann Institute for artwork. I.Y. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. I.A. is supported by the Chan Zuckerberg Initiative; an HHMI International Scholar award; a Merck KGaA, Darmstadt, Germany, research grant; European Research Council Consolidator Grant (ERC-COG) 724471-HemTree2.0; the Thompson Family Foundation; an MRA Established Investigator Award (509044); an Eden and Steven Romick Professorial Chair and Eden and Steven Romick Post-Doctoral Fellowship Fund; the Israel Science Foundation (703/15); the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine; the Helen and Martin Kimmel award for innovative investigation; the NeuroMac DFG/Transregional Collaborative Research Center Grant; an International Progressive MS Alliance/NMSS PA-1604-08459; and an Adelis Foundation grant. I.A. is the incumbent of the Alan and Laraine Fischer Career Development Chair. R.D. is supported by a Teva Pharmaceutical Industries research grant, the Rising Tide Translation Cancer Research Fund, a Melanoma Research Alliance (MRA) Young Investigator Award, an Israel Cancer Research Fund (ICRF) Research Career Development Award, an Israel Cancer Association Research Grant, the Mizutani Foundation for Glycoscience, the Emerson Collective Cancer Research Fund, an Israel Science Foundation (ISF) Individual Research Grant, the Moross Integrated Cancer Center, a Harry J. Lloyd Trust Career Development Award, Flight Attendant Medical Research Institute (FAMRI) Research Grants, the Ira and Diana Riklis Fund for CAR-T Therapy, the Enoch Foundation, the Pearl Welinsky Merlo Foundation and the Benoziyo Fund for the Advancement of Science, and by a grant from Gerty Schwarz Schaier. R. D. is the incumbent of the Rina Gudinski Career Development Chair.

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Correspondence to Ido Amit.

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Yofe, I., Dahan, R. & Amit, I. Single-cell genomic approaches for developing the next generation of immunotherapies. Nat Med 26, 171–177 (2020).

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