Targeting CD205 with the antibody drug conjugate MEN1309/OBT076 is an active new therapeutic strategy in lymphoma models
| Autor: | Chiara Tarantelli, Giulio Sartori, Emanuele Zucca, Monica Binaschi, Francesca Guidetti, Filippo Spriano, Renzo Lucchini, Gaetanina Golino, Anastasios Stathis, Roberta Pittau Bordone, Eugenio Gaudio, Georg Stussi, Rachel L. Dusek, Luciano Cascione, Alessandro Bressan, Davide Rossi, Christian Rohlff, Arnima Bisht, Mario Bigioni, Robert S. Boyd, Andrea Pellacani, Nickolas Attanasio, Francesco Bertoni, Afua Adjeiwaa Mensah, Merlino Giuseppe, Elena Bernasconi, Alessio Fiascarelli, Alberto J. Arribas |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Antibody-drug conjugate medicine.drug_class business.industry Venetoclax Hematology Monoclonal antibody medicine.disease Article Lymphoma 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Targeted drug delivery In vivo hemic and lymphatic diseases 030220 oncology & carcinogenesis medicine Cancer research Rituximab business Diffuse large B-cell lymphoma medicine.drug |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2019.227215 |
| Popis: | Antibody drug conjugates represent an important class of anti-cancer drugs in both solid tumors and hematological cancers. Here, we report preclinical data on the anti-tumor activity of the first-in-class antibody drug conjugate MEN1309/OBT076 targeting CD205. The study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination and validation experiments on in vivo models. CD205 was first shown frequently expressed in lymphomas, leukemias and multiple myeloma by immunohistochemistry on tissue microarrays. Anti-tumor activity of MEN1309/OBT076 as single agent was then shown across 42 B-cell lymphoma cell lines with a median IC50 of 200 pM and induction of apoptosis in 25/42 (59.5%) of the cases. The activity appeared highly correlated with its target expression. After in vivo validation as the single agent, the antibody drug conjugate synergized with the BCL2 inhibitor venetoclax, and the anti-CD20 monoclonal antibody rituximab. The first-in-class antibody drug targeting CD205, MEN1309/OBT076, demonstrated strong pre-clinical anti-tumor activity in lymphoma, warranting further investigations as a single agent and in combination. |
| Databáze: | OpenAIRE |
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