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Haematologica. 2019 Feb 7. pii: haematol.2018.211011. doi: 10.3324/haematol.2018.211011. [Epub ahead of print]

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

Author information

1
ImmunoGen, Inc.
2
Università della Svizzera italiana, Institute of Oncology Research.
3
Oncology Institute of Southern Switzerland.
4
Ente Ospedaliero Cantonale.
5
Università della Svizzera italiana, Institute of Oncology Research; frbertoni@mac.com.

Abstract

Antibody-drug conjugates (ADCs) are a novel way to deliver potent cytotoxic compounds to cells expressing a specific antigen. Four ADCs 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, TP53 inactivation or lymphoma histology. In conclusion, huB4-DGN462 is an attractive candidate for clinical investigation in patients with B-cell malignancies.

KEYWORDS:

Aggressive Non-Hodgkin's Lymphoma; CD19; SAR3419; antibody drug conjugate; leukemia

PMID:
30733273
DOI:
10.3324/haematol.2018.211011
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