Antibody-maytansinoid conjugates for the treatment of myeloma

被引:52
作者
Lutz, Robert J. [1 ]
Whiteman, Kathleen R. [1 ]
机构
[1] ImmunoGen Inc, Waltham, MA USA
关键词
cancer; myeloma; antibody; immunoconjugate; CD56; CD138; maytansinoid; IMGN901; BT062; CELL-ADHESION MOLECULE; MULTIPLE-MYELOMA; PLASMA-CELLS; GEMTUZUMAB OZOGAMICIN; MONOCLONAL-ANTIBODIES; IN-VITRO; EXPRESSION; CANCER; IMMUNOCONJUGATE; CHEMOTHERAPY;
D O I
10.4161/mabs.1.6.10029
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite recent advances in the treatment of multiple myeloma, new agents are still needed to improve the outcome for patients. The established success of monoclonal antibodies in the treatment of some cancers has promoted interest in developing antibody-based therapies for multiple myeloma. Efforts have included the development of antibodies conjugated to potent cytotoxic moieties that combine the specificity of anti-myeloma-targeting antibodies with highly active anti-tumor compounds. Two such immunoconjugates currently in clinical development are composed of antibodies that target cell surface proteins found on multiple myeloma cells, and are coupled to cytotoxic maytansinoids. IMGN901 targets the neural cell adhesion molecule, CD56, which is expressed on the majority of myeloma cells, as well as on other cancers, while BT062 targets CD138, a primary diagnostic marker for multiple myeloma. In this review, we discuss the preclinical and early clinical data for these two promising new antibody-based anti-myeloma agents.
引用
收藏
页码:548 / 551
页数:4
相关论文
共 35 条
[1]  
[Anonymous], 2008, Cancer facts and figures
[2]   A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma [J].
Attal, M ;
Harousseau, JL ;
Stoppa, AM ;
Sotto, JJ ;
Fuzibet, JG ;
Rossi, JF ;
Casassus, P ;
Maisonneuve, H ;
Facon, T ;
Ifrah, N ;
Payen, C ;
Bataille, R .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (02) :91-97
[3]  
Bross PF, 2001, CLIN CANCER RES, V7, P1490
[4]  
CHANANKHAN AA, ASH ANN M 2008, V112, P3689
[5]   Targeted cancer therapy: Conferring specificity to cytotoxic drugs [J].
Chari, Ravi V. J. .
ACCOUNTS OF CHEMICAL RESEARCH, 2008, 41 (01) :98-107
[6]   High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma [J].
Child, JA ;
Morgan, GJ ;
Davies, FE ;
Owen, RG ;
Bell, SE ;
Hawkins, K ;
Brown, J ;
Drayson, MT ;
Selby, PJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (19) :1875-1883
[7]  
Chilosi M, 1999, MODERN PATHOL, V12, P1101
[8]   Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation [J].
Ely, SA ;
Knowles, DM .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (04) :1293-1299
[9]   Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing [J].
Erickson, HK ;
Park, PU ;
Widdison, WC ;
Kovtun, YV ;
Garrett, LM ;
Hoffman, K ;
Lutz, RJ ;
Goldmacher, VS ;
Blättler, WA .
CANCER RESEARCH, 2006, 66 (08) :4426-4433
[10]  
GRIFFIN JD, 1983, J IMMUNOL, V130, P2947