Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo.
We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct anti-tumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.
Lentzsch
S
S
Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
LeBlanc
R
R
Podar
K
K
Davies
F
F
Lin
B
B
Hideshima
T
T
Catley
L
L
Stirling
D I
DI
Anderson
K C
KC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000187:drug effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D015996:Survival Rate; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D020533:Angiogenesis Inhibitors; D007166:Immunosuppressive Agents; D013792:Thalidomide