Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

Leukemia. 2003 Jan;17(1):41-4. doi: 10.1038/sj.leu.2402745.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / pathology
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Injections, Intraperitoneal
  • Mice
  • Mice, Nude
  • Microcirculation / drug effects
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / prevention & control*
  • Neovascularization, Pathologic / drug therapy*
  • Survival Rate
  • Thalidomide / analogs & derivatives
  • Thalidomide / therapeutic use*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology


  • Angiogenesis Inhibitors
  • Immunosuppressive Agents
  • Thalidomide