A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

Maria Eugénia Marques Da Costa, Sakina Zaidi, Jean Yves Scoazec, Robin Droit, Wan Ching Lim, Antonin Marchais, Jerome Salmon, Sarah Cherkaoui, Raphael J. Morscher, Anouchka Laurent, Sébastien Malinge, Thomas Mercher, Séverine Tabone-Eglinger, Isabelle Goddard, Francoise Pflumio, Julien Calvo, Francoise Redini, Natacha Entz-Werlé, Aroa Soriano, Alberto VillanuevaStefano Cairo, Pascal Chastagner, Massimo Moro, Cormac Owens, Michela Casanova, Raquel Hladun-Alvaro, Pablo Berlanga, Estelle Daudigeos-Dubus, Philippe Dessen, Laurence Zitvogel, Ludovic Lacroix, Gaelle Pierron, Olivier Delattre, Gudrun Schleiermacher, Didier Surdez, Birgit Geoerger

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    Abstract

    Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.

    Original languageEnglish
    Article number949
    JournalCommunications Biology
    Volume6
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2023

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