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Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies
Open accessAbstract
Antibody-targeted chemotherapy with gemtuzumab ozogamicin (CMA-676, a CD33-targeted immunoconjugate of N-acetyl-γ-calicheamicin dimethyl hydrazide [CalichDMH], a potent DNA-binding cytotoxic antitumor antibiotic) is a clinically validated therapeutic option for patients with acute myeloid leukemia (AML). Here, we describe the preclinical profile of another immunoconjugate of CalichDMH, CMC-544, targeted to CD22 expressed by B-lymphoid malignancies. CMC-544 comprises a humanized IgG4 anti-CD22 monoclonal antibody (mAb), G5/44, covalently linked to CalichDMH via an acid-labile 4-(4′-acetylphenoxy) butanoic acid (AcBut) linker. Both CMC-544 and unconjugated G5/44 bound human CD22 with subnanomolar affinity. CMC-544, but not unconjugated G5/44, exerted potent cytotoxicity against CD22+ B-cell lymphoma (BCL) cell lines (inhibitory concentration of 50%: 6-600 pM CalichDMH). CMC-544 caused a potent inhibition of growth of small but established BCL xenografts leading to cures (therapeutic index > 10). CMC-544 prevented the establishment of BCL xenografts and also caused regression of large BCLs (> 1.5 g tumor mass). In contrast, unconjugated CalichDMH, unconjugated G5/44, and an isotype-matched control conjugate, CMA-676, were ineffective against these BCL xenografts. Thus, CD22-targeted delivery of CalichDMH is a potent and effective preclinical therapeutic strategy for BCLs. The strong antitumor profile of CMC-544 supports its clinical evaluation as a treatment option for B-lymphoid malignancies.
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Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000) · Nature Medicine · doi:10.1038/74704 · Cited by 2,768
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Metadata
- Authors
- DiJoseph, J. F., Armellino, D. C., Boghaert, E. R., Khandke, K., Dougher, M. M., Sridharan, L., Kunz, A., Hamann, P. R., Gorovits, B., Udata, C., Moran, J. K., Popplewell, A. G., Stephens, S., Frost, P., & Damle, N. K.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-03-01
- Volume
- 103
- Issue
- 5
- Pages
- 1807-1814
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2113426218
- Cited by
- 361
- References
- 1
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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- DiJoseph, J. F., Armellino, D. C., Boghaert, E. R., Khandke, K., Dougher, M. M., Sridharan, L., Kunz, A., Hamann, P. R., Gorovits, B., Udata, C., Moran, J. K., Popplewell, A. G., Stephens, S., Frost, P., & Damle, N. K. (2004). Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. https://doi.org/10.1182/blood-2003-07-2466
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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