142 Enhanced antitumoral activity of HER2-CAR-Ts in comparison to trastuzumab in a live cell imaging supported 3D assay

Background Although most breast cancer patients are treated these days with a curative intention, there still many progressing to metastatic disease. The advent of anti-HER2 therapy has prominently prolonged the time disease progression and survival for those patients, where decent proportion is suffering from HER2+ tumor. Beside classical approaches via antibodies against HER2, use Chimeric Antigen Receptor T (CAR-T) cells also in solid context getting more attention. Methods In our study we evaluated efficacy Trastuzumab targeting CAR-T panel human cell lines (SK-OV3, Hs578T JIMT-1) different HER2 expression levels. tumor were seeded presence or absence immune (PBMC, monocytes, NK cells) cultured as 3D spheroids matrix-based system. growth if applicable invasion was measured fluorescence-based live imaging. On last experiment day, metabolic read-out (CellTiter-Glo, CTG assay) performed. Results inhibited dose-dependent manner line SK-OV3. increased specifically when added culture. positive JIMT-1 resistant treatment, which published data. model derived Trastuzumab-refractory patient. Interestingly, addition induced marked increase activity this well. targeted CART eradicated SK-OV3 well manner. untransduced control did not influence at all. HER2- served negative experiments, proved be any treatment study. Taken together imaging platform feasible tool testing biologics cellular therapies. Conclusions Our house developed specific effective eradicating cells. mechanism behind modulated sensitivity HER2-targeted will help shed some light possible resistance hopefully have translational value