Grace X. Y. Zheng

DINOcell: learning generalizable perturbation effects through self-distillation

J Li, Nilgun Tasdemir, Sofia Kyriazopoulou Panagiotopoulou, Sophie Xu et autres

A bstract Predicting cellular responses to therapeutics is a promising approach for novel target discovery. However, state-of-the-art computational models designed to predict perturbation effects struggle to generalize and outperform simple baselines. We present DINOcell, a weakly supervised framework that adapts self-distillation to …

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334 Computational mapping of CAR-T cell exhaustion through single-cell perturbation screens

Li Wang, David DeTomaso, Ashley A. Cass, Julie C. Chow et autres

Background While CAR-T cell therapies in hematologic cancers have shown great promise, in solid tumors additional cell engineering will be required to overcome T cell exhaustion, insufficient persistence and the inhibitory tumor microenvironment. We have developed T cell engineering and automation platforms …

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Improving Reliability of Immunological Assays by Defining Minimal Criteria for Cell Fitness

Sabine M. Ivison, Gabrielle Boucher, Grace X. Y. Zheng, Rosa V. Garcia et autres

Human PBMC-based assays are often used as biomarkers for the diagnosis and prognosis of disease, as well as for the prediction and tracking of response to biological therapeutics. However, the development and use of PBMC-based biomarker assays is often limited by poor …

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Abstract 7034: Pooled CRISPR screening coupled with single-cell sequencing identifies modifiers of CAR T cell state in the context of chronic antigen stimulation

Sahil Joshi, Glenn G. Wozniak, John D Gagnon, Kristina Vucci et autres

Abstract T cell exhaustion resulting from chronic antigen stimulation and an immunosuppressive tumor microenvironment limits the efficacy of T cell therapies in the solid tumor setting. The onset of T cell exhaustion is associated with distinct epigenetic and transcriptional changes. We hypothesized …

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Abstract 7042: Enhancing TCR T cell function in solid tumors through in vivo combinatorial screens and single-cell analysis

Dina Polyak, Jessica M. Fuhriman, Josephine Susanto, Allyson J. Merrell et autres

Abstract The therapeutic potential of T cell therapies for treating solid tumors can be limited by intrinsic T cell exhaustion mechanisms and the suppressive tumor microenvironment. To better understand these challenges and identify genetic perturbations to enhance T cell functions, we developed …

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WangLab at MEDIQA-Chat 2023: Clinical Note Generation from Doctor-Patient Conversations using Large Language Models

John Giorgi, Augustin Toma, Ronald Xie, Sondra Chen et autres

This paper describes our submission to the MEDIQA-Chat 2023 shared task for automatic clinical note generation from doctor-patient conversations. We report results for two approaches: the first fine-tunes a pre-trained language model (PLM) on the shared task data, and the second uses …

WangLab at MEDIQA-Chat 2023: Clinical Note Generation from Doctor-Patient Conversations using Large Language Models

John Giorgi, Augustin Toma, Ronald Xie, Sondra Chen et autres

This paper describes our submission to the MEDIQA-Chat 2023 shared task for automatic clinical note generation from doctor-patient conversations.We report results for two approaches: the first fine-tunes a pre-trained language model (PLM) on the shared task data, and the second uses few-shot …

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Abstract 1701: Single-cell multi-omic profiling and clonal tracing of the human gynecological tumor microenvironment

Vincent Liu, Katalin D. Sandor, Bence Dániel, Lionel Berthoin et autres

Abstract Tumor initiation and progression are the result of a close interplay between malignant cells and immune cells. While single-cell genomics has enabled the molecular dissection of the cellular heterogeneity underlying complex cancers, many facets of tumor microenvironments remain unresolved. In particular, …

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Abstract 2830: Multiplexed shRNAs targeting FAS and PTPN2 enhance CAR T persistence and anti-tumor efficacy

John D Gagnon, Adam J. Litterman, Jason A. Hall, Dina Polyak et autres

Abstract Cell therapies have shown limited efficacy in solid tumors, in part due to limitations in CAR T cell survival, expansion, and resistance to immunosuppressive pathways operating in the tumor microenvironment (TME). To overcome these hurdles, we screened a library of 171 …

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Abstract 2840: Identification of a safe harbor CRISPR-Cas9 integration site for improved cell therapy safety and potency

Grace X. Y. Zheng, Somya Khare, Brendan Galvin, Robby Moot et autres

Abstract T cell therapies for cancer have shown striking clinical efficacy in different tumor settings. Integration of a transgene cassette expressing an antigen receptor into the genome enables T cells to recognize specific tumor antigens. Viral vectors and transposons can introduce transgenes …

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213 AB-X integrated circuit T cells demonstrate improved potency, expansion, and specificity compared to MSLN CAR T cells

Stephen W. Santoro, Aaron R. Cooper, Natalie Bezman, Jun Feng et autres

Background In solid tumors, CAR T cell efficacy is limited by off-tumor toxicity and suppression by the tumor microenvironment (TME). AB-X is an integrated circuit T cell (ICT cell) intended for the treatment of ovarian cancer. AB-X includes a transgene cassette with …

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Integrated Single-Cell Transcriptomics and Chromatin Accessibility Analysis Reveals Regulators of Mammary Epithelial Cell Identity

Nicholas Pervolarakis, Quy Nguyen, Justice W. Williams, Yanwen Gong et autres

The mammary epithelial cell (MEC) system is a bilayered ductal epithelium of luminal and basal cells, maintained by a lineage of stem and progenitor populations. Here, we used integrated single-cell transcriptomics and chromatin accessibility analysis to reconstruct the cell types of the …

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