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Targeting CD19 with SAR3419, an anti-CD19-Maytansinoid Conjugate for the Treatment of B Cell Malignancies

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Antibody-Drug Conjugates and Immunotoxins

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

CD19 is a 95 kDa type 1 transmembrane glycoprotein whose expression is highly restricted to cells of B-lineage. CD19 expression is maintained in B-lineage cells that have undergone malignant transformation. Several approaches to exploit anti-CD19 monoclonal antibodies to treat B cell malignancies are being evaluated, including “naked” antibodies, bispecific antibodies, and immunoconjugates. SAR3419 is an ADC that is composed of a humanized monoclonal IgG1 anti-CD19 antibody (huB4) attached to a highly potent cytotoxic agent, the maytansinoid DM4, a tubulin agent, through reaction with a disulfide-containing linker. SAR3419 displays potent in vitro cytotoxicity towards CD19-positive lymphoma cell lines and shows good efficacy in several different in vivo models of lymphoma, including Burkitt’s lymphoma and diffuse large B cell lymphoma implanted into SCID mice. Initial clinical evaluation of SAR3419 was done in two phase I dose escalation studies exploring alternative schedules of administration, every 3 weeks and weekly, in patients with refractory/relapsed B cell non-Hodgkin’s lymphoma expressing CD19. Preliminary clinical activity is encouraging for its future development, with objective responses seen in both indolent and aggressive lymphomas in both phase I studies. There was a low incidence of clinically significant hematological toxicity, and the reversible ocular toxicity that defined the DLT on the 3-week schedule appeared to be manageable on weekly dosing regimens. The potential of SAR3419 is now being evaluated in a multi-trial phase II program which started in the second half of 2011.

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Authors and Affiliations

  1. ImmunoGen, Inc., 830 Winter Street, Waltham, MA, 02451, USA

    John M. Lambert

  2. Sanofi Oncology, Vitry sur Seine, France

    Veronique Blanc, Nathalie Le Bail & Anne Bousseau

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  1. John M. Lambert
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  2. Veronique Blanc
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Correspondence to John M. Lambert .

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    Gail Lewis Phillips

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Lambert, J.M., Blanc, V., Le Bail, N., Bousseau, A. (2013). Targeting CD19 with SAR3419, an anti-CD19-Maytansinoid Conjugate for the Treatment of B Cell Malignancies. In: Phillips, G. (eds) Antibody-Drug Conjugates and Immunotoxins. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5456-4_9

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  • DOI: https://doi.org/10.1007/978-1-4614-5456-4_9

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