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
; 104(8): 1633-1639, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30733273
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia
/
Imunoconjugados
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Antígenos CD19
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Anticorpos Monoclonais Humanizados
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Linfoma
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Maitansina
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Antineoplásicos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos