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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antigens, CD19 / metabolism*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Leukemia / drug therapy
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Lymphoma / drug therapy
  • Lymphoma / metabolism*
  • Lymphoma / pathology
  • Maytansine / analogs & derivatives*
  • Maytansine / chemistry
  • Maytansine / pharmacology
  • Mice
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal, Humanized
  • Antigens, CD19
  • Antineoplastic Agents
  • Immunoconjugates
  • Maytansine
  • coltuximab ravtansine