The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models
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
Affiliations
Stuart W. Hicks
ImmunoGen Inc., Waltham, MA, USA
Chiara Tarantelli
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland
Alan Wilhem
ImmunoGen Inc., Waltham, MA, USA
Eugenio Gaudio
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland
Min Li
ImmunoGen Inc., Waltham, MA, USA
Alberto J. Arribas
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland
Filippo Spriano
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland
Roberta Bordone
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Luciano Cascione
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland;Swiss Institute of Bioinformatics, Lausanne, Switzerland and
Katharine C. Lai
ImmunoGen Inc., Waltham, MA, USA
Qifeng Qiu
ImmunoGen Inc., Waltham, MA, USA
Monica Taborelli
Cytogenetics Laboratory, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Davide Rossi
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland;Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Georg Stussi
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Emanuele Zucca
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Anastasios Stathis
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
Callum M. Sloss
ImmunoGen Inc., Waltham, MA, USA
Francesco Bertoni
Università della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland
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.
