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Updated: Dec 2, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Targeting CD205 with the antibody drug conjugate MEN1309/OBT076 is an active new therapeutic strategy in lymphoma
Eugenio Gaudio1, Chiara Tarantelli1, Filippo Spriano1
1Università della Svizzera italiana, Istituto Oncologico di Ricerca, Bellinzona, Switzerland.
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.
Insights
The novel antibody drug conjugate MEN1309/OBT076 targeting CD205 shows significant preclinical anti-tumor activity in lymphoma. This first-in-class agent warrants further investigation as a single therapy and in combination treatments.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Antibody drug conjugates (ADCs) are a crucial class of anti-cancer therapeutics for various malignancies.
- CD205 is frequently expressed in hematological cancers, including lymphomas, leukemias, and multiple myeloma.
Purpose of the Study:
- To evaluate the preclinical anti-tumor activity of MEN1309/OBT076, a novel ADC targeting CD205.
- To assess the efficacy of MEN1309/OBT076 as a single agent and in combination with other therapies.
Main Methods:
- In vitro screening of MEN1309/OBT076 across 42 B-cell lymphoma cell lines.
- Immunohistochemistry analysis of CD205 expression in hematological cancers.
- In vivo validation studies and combination experiments with venetoclax and rituximab.
Main Results:
- MEN1309/OBT076 demonstrated potent in vitro activity with a median IC50 of 200 pM and induced apoptosis in 59.5% of tested lymphoma cell lines.
- Anti-tumor activity strongly correlated with CD205 target expression.
- MEN1309/OBT076 showed synergistic effects when combined with venetoclax and rituximab in vivo.
Conclusions:
- MEN1309/OBT076 exhibits significant preclinical anti-tumor efficacy in lymphoma models.
- This first-in-class CD205-targeting ADC holds promise for further clinical development.
- Combination strategies involving MEN1309/OBT076 may enhance therapeutic outcomes in hematological malignancies.
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