DEC 06, 2018 7:00 AM PST

Image-based screening for precision medicine and immunotherapy

Sponsored by: PerkinElmer
C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • CSO and Scientific Co-founder, Allcyte GmbH
    Biography
      Gregory Vladimer is the CSO and a scientific co-founder of Allcyte in Vienna, Austria, where high-throughput and high-content confocal microscopy of primary patient samples is used in order to define drug action at single cell resolution. Dr. Vladimer received his PhD in immunology from the Program in Innate Immunity of the Department of Medicine at the University of Massachusetts Medical School, prior to his postdoctoral work at the Center for Molecular Medicine, CeMM, of the Austrian Academy of Sciences. Dr. Vladimer and his colleagues performed what they believe was the first prospective study assessing the feasibility and efficacy of ex vivo drug-response profiling to guide personalised treatment selection across large panels of possible treatments for patients suffering aggressive haematological malignancies, published at the interim stage last year in Lancet Haematology. The methodology for the screening was invented by a team of scientists who met at CeMM including Prof. Dr. Berend Snijder, Dr. Nikolaus Krall, and Prof. Dr. Giulio Superti-Furga. The team is now focused on determining the feasibility of deploying such image-based single-cell screening assays into the clinical realm for patients with various malignancies. Dr. Vladimer has received numerous grants and fellowships on his work and has publications in NEJM, Nature, Immunity, Cell, Science, Nature Chemical Biology, PNAS, amongst others.

    Abstract

    DATE: December 06, 2018
    TIME: 15:00 GMT, 16:00 CET, 10:00 EST, 07:00 PST

    High-throughput confocal microscopy has changed the way drug screening can be performed, by enabling the detection of single-cell phenotypes after small molecule or biological perturbation. Combined with advances in image analysis, which have allowed for the quantification of these single cell events, it opens new doors for large phenotype-focused studies. However, these technologies have historically been used with adherent cell lines. By amending these technologies to non-adherent cells, we can perform image-based screening directly in primary material, enabling more clinically translatable drug screening, and ultimately, functional precision medicine. An ongoing clinical trial, from the Center of Molecular Medicine of the Austrian Academy of Sciences and the Medical University of Vienna, combined multiparametric immunofluorescence with high-throughput automated microscopy and single cell image analysis, to quantify tumor-cell specific biological parameters of millions of adherent and non-adherent individual cells from primary samples to prioritize treatment options for patients with late-stage hematological malignancies. An interim analysis revealed that patients receiving treatment prioritized by this program had a longer progression-free survival on this therapy than the prior round of therapy. This style screening can be further combined with epigenetic screening to rationally uncover combination treatment options for specific indications. Lastly, using images of multi-lineage cells from the haematological system, and novel statistical algorithms, we can quantify the propensity of cells to physically interact with each other, thereby mapping the effect of ex vivo stimuli on immune responses, and potentially uncover new immunomodulatory drugs.

    Learning Objectives:

    • How functional precision medicine can be enabled through single-cell image based screening of malignant patient material,
    • How the combination of functional screening through high-throughput imaging and genetics can reveal clinically relevant drug combinations that may be missed by using single-screening approaches,
    • How mapping physical immune responses through cell-to-cell contacts revealed in images can show unknown mechanisms of drugs.

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