|
|
Blood, 15 August 2008, Vol. 112, No. 4, pp. 1329-1337.
Prepublished online as a Blood First Edition Paper on October 9, 2007September 28, 2007; DOI 10.1182/blood-2007-08-107292.
 Previous Article | Next Article 
Submitted August 15, 2007
Accepted September 23, 2007
Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu
Yu-Tzu Tai*, Myles Dillon, Weihua Song, Merav Leiba, Xian-Feng Li, Peter Burger, Alfred Ian Lee, Klaus Podar, Teru Hideshima, Audie G Rice, Anne van Abbema, Lynne Jesaitis, Ingrid Caras, Debbie Law, Edie Weler, Wanling Xie, Paul Richardson, Nikhil C Munshi, Herve Avet-Loiseau, Daniel E.H. Afar, and Kenneth C Anderson
The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Department of Research, PDL BioPharma Inc., Fremont, CA, United States
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States
VA Healthcare System, Department of Medicine, Harvard Medical School, Boston, MA, United States
Laboratoire d'Hematologie, Institut de Biologie, Nantes, France
* Corresponding author; email: yu-tzu_tai{at}dfci.harvard.edu.
Currently there are no approved monoclonal antibody (mAb) therapies for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (>97%) with low levels of circulating CS1 detectable in MM patient sera, but not in normal donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. van Rhee, S. M. Szmania, M. Dillon, A. M. van Abbema, X. Li, M. K. Stone, T. K. Garg, J. Shi, A. M. Moreno-Bost, R. Yun, et al.
Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma
Mol. Cancer Ther.,
September 1, 2009;
8(9):
2616 - 2624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-T. Tai, E. Soydan, W. Song, M. Fulciniti, K. Kim, F. Hong, X.-F. Li, P. Burger, M. J. Rumizen, S. Nahar, et al.
CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells
Blood,
April 30, 2009;
113(18):
4309 - 4318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
