Ferreira, Nathalia and Agorku, David and Rosa, Andre and Roosz, Julia and Christ, Lena and Anderle, Nicole and Kulkarni, Ajinkya and Hussein, Abir and Sayedipour, Sana S. and Luna, Omar F. and Legler, Tobias and Strobel, Philipp and Albericio, Fernando and Cruz, Luis and Beckhove, Phillipp and Loskill, Peter and Alves, Frauke and Markus, M. Andrea and Ramos-Gomes, Fernanda (2026) Advanced Human Immune Cell-Organoid Co-Cultures for Functional Testing of Cancer Nanovaccines. ADVANCED SCIENCE, 13 (10). e15199. ISSN 2198-3844
Full text not available from this repository. (Request a copy)Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a major clinical challenge due to late detection and limited treatment responsiveness. To better evaluate complex immunotherapies in a human-relevant setting, we developed an integrated organoid-immune co-culture pipeline using PDAC patient-derived organoids (PDOs) and matched HLA immune cells. As a proof of concept, we assessed an MSLN-targeted nanovaccine (Mesovac), alone and in combination with FOLFIRINOX chemotherapy and Atezolizumab. We evaluated Mesovac across a multi-stage pipeline, including T-cell stimulation, ex vivo expansion, and PDO-immune co-cultures, to assess immune activation, specificity, and synergy with combinatorial treatments. MSLN-stimulated T-cells, derived from PDAC patients, showed increased IFN-gamma production and selective infiltration into MSLN-expressing PDOs. Artificial antigen-presenting cells (aAPCs) boosted the expansion of reactive T-cells, enhancing antitumor responses. Notably, combining Mesovac with FOLFIRINOX and Atezolizumab maintained PD-L1+ T-cell levels and reduced cancer stem cells and aggressive PDAC subsets. Using this advanced in vitro workflow, we highlight that this platform, using human organoid-immune cell co-cultures, enables the evaluation of complex processes related to nanovaccine strategies that would not be possible in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PANCREATIC ADENOCARCINOMA; T-CELLS; MESOTHELIN; ANTIGEN; EXPRESSION; VACCINE; IMMUNOTHERAPY; SAFETY; cancer vaccine; immunotherapy; mesothelin; organoids; PDAC |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2026 05:12 |
| Last Modified: | 15 Apr 2026 05:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67429 |
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