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Haematologica. 2020 Jan 9. pii: haematol.2019.227215. doi: 10.3324/haematol.2019.227215. [Epub ahead of print]

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

Author information

1
Università della Svizzera italiana, Istituto Oncologico di Ricerca, Bellinzona, Switzerland.
2
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
3
Menarini Ricerche S.p.A., Pomezia, Italy.
4
Lab of Diagnostica Molecolare, Dept of Medicina di Laboratorio EOLAB, Bellinzona, Switzerland.
5
Oxford BioTherapeutics, Ltd., Abingdon, UK.
6
Oxford BioTherapeutics, Inc., San Jose, CA, USA.
7
Menarini Ricerche S.p.A - Menarini Group, Florence, Italy.
8
Università della Svizzera italiana, Istituto Oncologico di Ricerca, Bellinzona, Switzerland; frbertoni@mac.com.

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.

KEYWORDS:

Aggressive Non-Hodgkin's Lymphoma; CD205; Molecular Pharmacology; diffuse large B cell lymphoma; rituximab

PMID:
31919082
DOI:
10.3324/haematol.2019.227215
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