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Haematologica. 2019 Aug;104(8):1633-1639. doi: 10.3324/haematol.2018.211011. Epub 2019 Feb 7.

The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models.

Author information

1
ImmunoGen Inc., Waltham, MA, USA.
2
UniversitĂ  della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland.
3
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
4
Swiss Institute of Bioinformatics, Lausanne, Switzerland and.
5
Cytogenetics Laboratory, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
6
ImmunoGen Inc., Waltham, MA, USA frbertoni@mac.com callum.sloss@immunogen.com.
7
UniversitĂ  della Svizzera italiana, Institute of Oncology Research, Bellinzona, Switzerland frbertoni@mac.com callum.sloss@immunogen.com.

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.

PMID:
30733273
DOI:
10.3324/haematol.2018.211011
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