Targeting CD205 with the antibody drug conjugate MEN1309/OBT076 is an active new therapeutic strategy in lymphoma models.

Abstract

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.

• Authors: Eugenio Gaudio, Chiara Tarantelli, Filippo Spriano, Francesca Guidetti, Giulio Sartori, Roberta Bordone, Alberto J Arribas, Luciano Cascione, Mario Bigioni, Giuseppe Merlino, Alessio Fiascarelli, Alessandro Bressan, Afua Adjeiwaa Mensah, Gaetanina Golino, Renzo Lucchini, Elena Bernasconi, Davide Rossi, Emanuele Zucca, Georg Stussi, Anastasios Stathis, Robert S Boyd, Rachel L Dusek, Arnima Bisht, Nickolas Attanasio, Christian Rohlff, Andrea Pellacani, Monica Binaschi, Francesco Bertoni
• Journal: Haematologica (Haematologica) Vol. 105 Issue 11 Pg. 2584-2591 (11 01 2020) ISSN: 1592-8721 [Electronic] Italy
• PMID: 33131247 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD20
• Antineoplastic Agents
• Immunoconjugates
• Rituximab

Topics

• Antibodies, Monoclonal (pharmacology)
• Antigens, CD20
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Cell Line, Tumor
• Humans
• Immunoconjugates (pharmacology, therapeutic use)
• Lymphoma (drug therapy)
• Rituximab (therapeutic use)