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SITC 2023 Poster 77

Analyzing Effects of Immunotherapies, Such as Bispecific Antibodies and Cellular Therapy, Targeting EGFR Expression With a High Content Screening Platform in Patient-derived Organoids

Saskia de Man, Chiara Foini, Tomas Veenendaal, Sergei Chavez Abiega, Michelle Kop, Rick Heeren, Christos Sarantaris, Daniel Okkes, Ashgard Weterings, Leo Price, Gera Goverse

Crown Bioscience, Leiden, The Netherlands

While several immunotherapies have shown promising results for specific cancer indications in the clinic, their full potential and mechanisms that regulate anti-tumor immune response remain to be uncovered.

With the development of patient-derived organoids (PDOs) used in advanced 3D co-cultures with immune cells, better preservation of the original patient tumor and reconstitution of complex cellular interactions that occur in the tumor microenvironment can be achieved.

In this study, a high content imaging (HCI)-based analysis that allows testing of cancer immunotherapies in a physiological relevant 3D screening platform is presented. As proof-of-concept, we target the well-known target EGFR with bispecific antibodies and CAR-T.

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  • How a tumor organoid – immune cell co-culture system in combination with HCI allows the detection and quantification of immune cell infiltration and killing effects on patient derived organoids across different cancer types and EGFR expression levels in a single assay.

  • How a broad spectrum of responses can be observed based on the tumor type and differential activation of PBMCs.

  • The effects of EGFR targeting immunotherapies such as bispecific antibodies and CAR T cells on enhanced killing or infiltration into organoids.

  • How testing of Immuno-oncology (IO) drugs in clinically relevant models, bring the promise of IO therapies to more indications and patients.

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