Humanized Patient-derived xenograft models for developing personalized therapy against Small Cell Lung Cancer
Bildiriler > Özet Bildiri
Yazarlar: H Rouhrazi, S Erdem, V Zafari, G Esmailnia, R Meuwissen
03.02 - Airway cell biology and immunopathology, , , Uluslararası, Özet Bildiri, ss 3524-3524
DOI: 10.1183/13993003.congress-2022.3524
Özet
Aim of our project is: -Fully characterize the cellular heterology in PDX SCLC by genetic analyses, specific growth and marker characteristics, as well as comparative genomic sequencing of individual PDX samples via Next Generation Sequencing. Whole exome and single cell transcriptome sequencing should reveal differences in genomic mutations and (mutated) transcript patterns between primary and relapsed, therapy resistant, SCLC. -We engineered 4 SCLC tumors with specific fluorescent labeled markers for respective epithelial and mesenchymal cell phenotypes. This will allow us to follow effect of epithelial-mesenchymal plasticity on SCLC growth and various therapy response. -Transfer of SCLC PDX models in humanized mice background, enabling growth of heterogeneous human SCLC in a reconstituted immune environment. First immuno therapy experiments will be carried out to the test if immunoediting efficacy changes, induced by immune checkpoint blockade effectors, are linked to nature and content of neoantigens in every individual SCLC lesion and in how far changes in neoantigen characteristics are linked with SCLC plasticity. At the end of this project, we expect that we will gain insight into some of the molecular pathways and mechanisms that refer rapid resistance to chemotherapy sensitivity of the different SCLC cell populations, and the role tumor plasticity plays in facilitating the phenotypic complexity of SCLC. Moreover, our new, humanized SCLC PDX models will be of valuable use for extensive drug screens and should thereby lead to discover new candidate genes that control some of these pivotal molecular pathways.