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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

📑 Check out our paper titled “Systematic discovery of CRISPR-boosted CAR T cell immunotherapies” at @Nature (open access): www.nature.com/articles/s41.... Feedback & suggestions are very welcome. (13/13)

Systematic discovery of CRISPR-boosted CAR T cell immunotherapies - Nature

CELLFIE, a CRISPR platform for optimizing cell-based immunotherapies, identifies gene knockouts that enhance CAR T cell efficacy using in vitro and in vivo screens.

www.nature.com

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🤝 This was a large project & great teamwork by: P. Datlinger*, E.V. Pankevich*, C.D. Arnold*, N. Pranckevicius, J. Lin, D. Romanovskaia, M. Schäfer, F. Piras, A.-C. Orts, A. Nemc, P. Biesaga, M. Chan, T. Neuwirth, A. Artemov, W. Li, S. Ladstätter, T. Krausgruber, C. Bock (12/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

⚕️ Our CELLFIE platform supports clinical translation of CRISPR-boosted CAR T cells. For example, to avoid the DNA double-strand breaks introduced by CRISPR knockout, we performed a tiling base-editing screen across RHOG and identified promising gRNA for clinical testing. (11/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🔥 What’s next? Our discovery of strong combined effects for RHOG & FAS knockout underlines the potential of synergistic gene edits for boosting CAR T cell function. We thus integrated combinatorial screening into CELLFIE, using the Blainey lab’s CROPseq-multi method. (10/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🔬 From a technical perspective, we are excited how our new in vivo CROP-seq method improves gRNA detection (reading from an mRNA transcript as in nature.com/articles/nme...) and reduces experimental noise (by using UMIs), which enables larger screens with fewer mice. (9/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

💪 We also observed prolonged survival for FAS knockout CAR T cells, likely because these cells are less effective at killing each other (“fratricide”). Combining RHOG & FAS knockout, we obtained more & better CAR T cells, which further improved survival in leukemic mice. (8/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🔍 RHOG is a small GTPase involved in cell signaling. How does it influence CAR T cells ? We found that RHOG knockout increases the proliferative capacity of CAR T cells and helps them retain a highly functional state with reduced exhaustion and enhanced memory phenotype. (7/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🐁 We performed extensive in vivo validations and found that RHOG knockout CAR T cells achieve strong reductions in cancer cell numbers and prolonged survival in an aggressive mouse model of human leukemia, with consistent results across different CARs and T cell donors. (6/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🐭 But not everything that makes CAR T cells proliferate or kill better in vitro translates into more effective therapies. For scalable validation in mice, we conducted pooled in vivo CRISPR screening and observed strong positive effects of RHOG, PRDM1, and FAS knockouts. (5/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

💡 Conceptually, our CRISPR screens create a form of “artificial evolution” by which we optimize CAR T cells for their tasks as cancer therapeutics. This is important because CAR T cells are products of cell engineering and lack task-specific evolutionary optimization. (4/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🩸 Using CELLFIE, we conducted 58 genome-wide CRISPR screens, with readouts for CAR T cell proliferation, target cell recognition, activation, apoptosis & fratricide, and exhaustion. The screens identified known genes (PD-1, CTLA4, TIM3, TIGIT etc.) and promising new hits. (3/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

⚙️ We developed CELLFIE (“cell engineering for immunotherapy enhancement”), a CRISPR platform to make & test gene-edited CAR T cells at scale. CELLFIE supports in vitro & in vivo screens with various clinically relevant readouts, plus combinatorial & base-editing screens. (2/13)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · 14d

🧬 CAR T cells demonstrate the power of engineered cells as therapeutics. But they fail for most patients. Can CRISPR help here? Our new paper in Nature (www.nature.com/articles/s41...) presents a screening platform to optimize immunotherapies & discover boosters of CAR T cell function. (1/13)

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Reposted by Christoph Bock Lab @ CeMM & MedUni Vienna

Myllia Biotechnology @mylliabio.bsky.social · 29d

We’re thrilled to announce that the "High-Content CRISPR Screening" conference will take place on March 18–19, 2026, in Vienna, Austria.

The registration is now open via the conference website:
lnkd.in/d8KACZy5

Meet the Speaker: Christoph Bock

@bocklab.bsky.social

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🚀 Check out the paper, dataset, and computational methods (open access | open data | open source):
📑 Paper: www.cell.com/cell-systems...
🧬 Dataset: macrophage-regulation.bocklab.org
💻 Code: github.com/epigen/macro...
Feedback & suggestions are very welcome. (9/9)

Integrated time-series analysis and high-content CRISPR screening delineate the dynamics of macrophage immune regulation

Traxler, Reichl, et al. combine multi-omics time series with high-content CRISPR screens to identify regulators of macrophage immune responses and map their functional similarities. This study reveals...

www.cell.com

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🤝 Great teamwork by: Peter Traxler*, Stephan Reichl*, Lukas Folkman, Lisa Shaw, Victoria Fife, Amelie Nemc, Djurdja Pasajlic, Anna Kusienicka, Daniele Barreca, Nikolaus Fortelny, André Rendeiro, Florian Halbritter, Wolfgang Weninger, Thomas Decker, Matthias Farlik, Christoph Bock (8/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🗺️ In summary, this study provides a blueprint of epigenetic & transcriptional dynamics and regulator functions underlying macrophage immune responses. We found it particularly useful to combine and integrate multi-omics time-series with high-content CRISPR screening. (7/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

💡 Biological detail: EP300-mediated repression of interferon-stimulated genes (ISGs), validated genetically & pharmacologically. Proposed mechanism: The histone acetyltransferase EP300 counteracts HDAC activity required for BRD4 availability for transcription elongation. (6/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🤖 We used machine learning to infer functional similarity maps of transcriptional regulators from the CROP-seq data, establishing a broadly applicable method to dissect transcriptional programs. (5/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

✂️ To disentangle causes and consequences, we performed high-content CRISPR screening (CROP-seq + CITE-seq) to perturb 135 regulators during Listeria infection. Our hits include: PU.1, JAK-STAT proteins, splicing factors (SFPQ, SF3B1) & epigenetic regulators (EP300, SMC1A). (4/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🧬 Integrative analysis revealed strong differences between interferon-driven (IFN-β/γ) and pathogen-driven (Listeria/LPS) trajectories. Many immune genes showed "epigenetic potential": pre-established open chromatin ready for rapid expression upon stimulation. #Epigenetics (3/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🦠 Pathogens & cytokines trigger macrophage receptors and induce immune gene expression. We challenged mouse macrophages (BMDMs) with 6 immune stimuli (Listeria, LCMV, Candida, LPS, IFN-β, IFN-γ) and profiled genes (RNA-seq) and chromatin (ATAC-seq) over six time points. (2/9)

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Aug 12

🛡️How do macrophages tailor their defenses to different pathogens? Our new paper in @cp-cellsystems.bsky.social combines dense multi-omics time series with high‐content CRISPR screens (CROP-seq) to map the regulatory landscape underlying macrophage immune responses: www.cell.com/cell-systems... (1/9)

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Reposted by Christoph Bock Lab @ CeMM & MedUni Vienna

CeMM @cemm.oeaw.ac.at · Aug 8

🧬How do #macrophages respond so quickly to pathogens?
A new study by CeMM & @meduniwien.ac.at researchers, led by @bocklab.bsky.social & @mfarlik.bsky.social, reveals key regulators of immune responses using gene editing & machine learning.

➡️ More info: bit.ly/40p5ABe
🔗 Study: bit.ly/4lwEAIm

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Christoph Bock Lab @ CeMM & MedUni Vienna @bocklab.bsky.social · Jul 18

🤝 Great collaboration between @bocklab.bsky.social (@moritzbaio.bsky.social, Animesh, Jake), @nonchev.bsky.social, @gxxxr.bsky.social, and pathologist Viktor Kölzer.

SpotWhisperer is at #ICML25 FM4LS workshop. Visit our poster on Saturday (19 July 2025) if you're interested & attending ICML. (6/6)

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