Article Figures & Data
Figures
- Figure 1.
Pattern of expression of CD19 and CD20 antigens during B-cell development and associated malignancies. A simplified cartoon of B-cell lineage, B-cell malignancies, and antigen expression (59, 60). The positioning of the different B-cell malignancies associated with different stages of B-cell development is abridged and illustrative only; a detailed description is beyond the scope of this review.
- Figure 2.
Structure of SAR3419. Figure is adapted from Al-Katib et al. (43).
- Figure 3.
Kinetics of pharmacodynamic markers p-histone H3 and cleaved caspase 3 (C-Caspase 3) in Ramos xenograft model. Quantitative evaluation of p-Histone H3 and C-Caspase 3 by image analysis quantification at 6, 24, 48, 72, and 96 hours after administration of a single intravenous dose of 20 mg/kg of SAR3419 in SCID mice bearing established Ramos subcutaneous xenograft tumors.
- Figure 4.
Kinetics of the production of nonproteic maytansinoid metabolites in the Ramos xenograft model. Quantitative evaluation of nonproteic maytansinoid metabolites (metabolites not linked to proteins) in nanograms per gram of tumor (ng Eq/g) at 2, 6, 8, 24, and 48 hours after administration of a single intravenous dose of 15 mg/kg of [3H]-SAR3419 in SCID mice bearing established Ramos xenograft tumors.
- Figure 5.
Impact of naked huB4 antibody on the efficacy of a single administration of SAR3419 against a bulky Ramos subcutaneous tumor xenograft model. SCID mice were inoculated with Ramos tumor cells, and once the xenografts had reached about 295 mm3 on day 11, mice (6 per group) were treated with a test article given by intravenous injection (tail vein). The huMy9-6 (anti-CD33 antibody) is an isotype-matched, nonspecific control humanized IgG1 antibody; huB4 is the anti-CD19 humanized IgG1 antibody moiety of SAR3419; huB4-DM4 is a synonym for SAR3419.
- Figure 6.
Longitudinal monitoring of SAR3419 activity using FDG-PET in mice inoculated intravenously with Daudi lymphoma. Samples of serial FDG-PET images obtained in mice bearing disseminated lymphoma treated on day 24 with SAR3419 or control treatment. The metabolic activity is coded on a color scale from blue (low radioactive tracer uptake) to red (high uptake). The tracer accumulates in elimination organs (urinary bladder), nonspecific sites (adipose tissues), and FDG-avid tumor tissues (depicted by white arrows).
Tables
- Table 1.
Clinical trials and discovery projects targeting CD19
Biologic compound Type Mechanism of action Phase (initiation date) MT-103 (blinatumomab) Micromet, Inc. Bispecific scFv anti-CD19/anti-CD3 BiTE T-cell recruitment and activation I/II/III (2007) Pivotal trial for MDR+ ALL SAR3419 Sanofi-Aventis/ImmunoGen, Inc. Humanized anti-CD19 mAb conjugated to maytansinoid DM4 ADC (tubulin binder) I/II (2007) MEDI-551 MedImmune/Astra-Zeneca Glycoengineered humanized anti-CD19 mAb (BioWa's Potelligent) Naked antibody high-affinity FcγRIII-enhanced ADCC I (2010) MOR-208/XmAb5574 Xencor/Morphosys Fc engineered humanized anti-CD19 mAb Naked antibody high-affinity FcγRIII-enhanced ADCC I (2010) MDX-1342 Medarex/Bristol-Myers Squibb Glycoengineered fully human anti-CD19 mAb (BioWa's Potelligent) Naked antibody high-affinity FcγRIII-enhanced ADCC I (2008, on hold) Combotox University of Texas Southwestern/Abiogen Mixture of chimeric anti-CD19 mAb HD37 and anti-CD22 mAb RFB4, both conjugated to deglycosylated ricin A-chain (HD37-dgA + RFB4-dgA) Immunotoxin conjugate with deglycosylated ricin A-chain I (2005) DI-B4Merck KGaA/Cancer Research UK Chimeric anti-CD19 mAb monoclonal antibody Naked antibody ADCC I (2010) SGN-19A Seattle Genetics Fully human anti-CD19 mAb (hBU12) conjugated to auristatin (vc-MMAE) ADC (tubulin binder) Discovery MDX-1206 Medarex/Bristol-Myers Squibb Fully human anti-CD19 mAb (MDX1435) conjugated to duocarmycin (vc-MGBAA) ADC (DNA alkylating agent) Discovery AFM-11 Affimed Therapeutics AG Tetravalent tandem antibody (TandAb) anti-CD19/anti-CD3 T-cell recruitment Discovery AFM-12 Affimed Therapeutics AG Tetravalent tandem antibody (TandAb) anti-CD19/anti-CD16 NK cell recruitment Discovery
Volume 17, Issue 20
Jump to section
- Article
- Abstract
- Introduction
- Monoclonal Antibodies beyond Rituximab for Treating B-Cell Malignancies
- CD19 Antigen
- Anti-CD19 Intervention
- SAR3419 Structure and Mechanism of Action
- SAR3419 Preclinical Activities in Different Lymphoma Models
- Imaging SAR3419 Activity in a Mouse Model
- SAR3419 Clinical Development
- Conclusions
- Disclosure of Potential Conflicts of Interest
- Acknowledgments
- References
- Figures & Data
- Info & Metrics