Integrated Workflow Solutions For The Early Screening Of Target Candidates For Immunotherapy Of Pancreatic Cancer

By Daniel Schaefer, Laura N. Küster, Julia Schüler, Melina Lamorte, Dorothee Lenhard, Philipp Ströbel, Frauke Alves, Andreas Bosio, Olaf Hardt

The development of successful therapeutics demands an accurate identification of biological targets. This is particularly challenging in cancer, where the effectiveness of novel immunotherapies, such as those based on chimeric antigen receptor (CAR) T cells, is hampered by the lack of suitable tumor-specific antigens. A valid model for systematic screenings of therapeutic targets is represented by primary tumor cells derived from patient-derived xenograft (PDX) and primary solid tumors.

However, a prior consideration of related experimental challenges is necessary. The dissociation of tissues to release intact individual cells with preserved surface antigen epitopes is a crucial step in every investigation of drug targets and biomarkers. Equally crucial is the purification of target human tumor cells from the mouse cell suspension, regardless of the cancer cell phenotype, for a systematic tumor-specific antigen expression analysis. It is of utmost importance to utilize tissue and cell preparation approaches which provide high-quality samples while still ensuring a quick, streamlined process. Last but not least, lack of proper analysis tools can slow down the target identification process. Screening of large numbers of targets with manual processing can not only be extremely laborious and time consuming, but also can result in poor-quality data that are often irreproducible.

To address all the challenges described above, our research teams combined automated methodologies for gentle tumor dissociation, immunomagnetic untouched isolation of tumor cells, and high-throughput flow-cytometric analysis from Miltenyi Biotec. As a result, we identified novel target candidates for immunotherapy of pancreatic cancer.