The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models
Year: 2019
Type: article
Abstract: Antibody-drug conjugates (ADC) are a novel way to deliver potent cytotoxic compounds to cells expressing a specific antigen. Four ADC targeting CD19, including SAR3419 (coltuximab ravtansine), have entered clinical development. Here, we present huB4-DGN462, a novel ADC based on the SAR3419 anti-CD19 antibody linked via sulfo-SPDB to the potent DNA-alkylating agent DGN462. huB4-DGN462 had improved in vitro anti-proliferative and cytotoxic activity compared to SAR3419 across multiple B-cell lymphoma and human acute lymphoblastic leukemia cell lines. In vivo experiments using lymphoma xenografts models confirmed the in vitro data. The response of B-cell lymphoma lines to huB4-DGN462 was not correlated with CD19 expression, the presence of BCL2 or MYC translocations, TP53 inactivation or lymphoma histology. In conclusion, huB4-DGN462 is an attractive candidate for clinical investigation in patients with B-cell malignancies.
Source: Haematologica
Authors: Stuart W. Hicks, Chiara Tarantelli, Alan Wilhem, Eugenio Gaudio, Min Li, Alberto J. Arribas, Filippo Spriano, Roberta Bordone, Luciano Cascione, Katharine C. Lai, Qifeng Qiu, Monica Taborelli, Davide Rossi, Georg Stussi, Emanuele Zucca, Anastasios Stathis, Callum M. Sloss, Francesco Bertoni
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
Funder: Fondazione Gelu
OpenAlex ID: W2912969574