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Cancer Therapy: Preclinical

Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206

Eric Sanchez, Mingjie Li, Cathy Wang, Cydney M. Nichols, Jennifer Li, Haiming Chen and James R. Berenson
Eric Sanchez
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Mingjie Li
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Cathy Wang
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Cydney M. Nichols
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Jennifer Li
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Haiming Chen
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James R. Berenson
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DOI: 10.1158/1078-0432.CCR-11-3130 Published July 2012
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Abstract

Purpose: Doxorubicin has shown efficacy especially in combination treatment for the treatment of multiple myeloma; however, its side effects limit its use. INNO-206 is an albumin-binding prodrug of doxorubicin, which is released from albumin under acidic conditions. Because INNO-206 has not been previously evaluated in any hematologic malignancy, we determined its anti–multiple myeloma effects.

Experimental Design: The anti–multiple myeloma effect of INNO-206 at different pH levels on multiple myeloma cell proliferation using multiple myeloma cell lines with the MTS assay and antiangiogenic activity using the chorioallantoic membrane/feather bud assay were determined. The anti–multiple myeloma effects and toxicity of INNO-206 were also compared with conventional doxorubicin and PEGylated liposomal doxorubicin (PLD) alone, and in combination with bortezomib, using our multiple myeloma xenograft models.

Results: INNO-206 inhibited blood vessel formation and reduced multiple myeloma cell growth in a pH-dependent fashion. INNO-206 alone produced marked anti–multiple myeloma effects in vivo at doses that doxorubicin was toxic, and the combination of INNO-206 plus bortezomib produced increased anti–multiple myeloma effects compared with either agent alone. In contrast, all mice receiving bortezomib with doxorubicin or PLD died.

Conclusions: These findings show that INNO-206 produces anti–multiple myeloma effects in vitro and in vivo. It also enhances the antitumor effects of bortezomib. These results suggest that INNO-206 may provide patients with multiple myeloma with an anthracycline that may be administered safely at higher doses compared with free doxorubicin, resulting in superior efficacy compared with the currently available anthracyclines to treat this B-cell malignancy. Clin Cancer Res; 18(14); 3856–67. ©2012 AACR.

  • Received December 8, 2011.
  • Revision received April 18, 2012.
  • Accepted May 10, 2012.
  • ©2012 American Association for Cancer Research.
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Clinical Cancer Research: 18 (14)
July 2012
Volume 18, Issue 14
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Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206
Eric Sanchez, Mingjie Li, Cathy Wang, Cydney M. Nichols, Jennifer Li, Haiming Chen and James R. Berenson
Clin Cancer Res July 15 2012 (18) (14) 3856-3867; DOI: 10.1158/1078-0432.CCR-11-3130

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Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206
Eric Sanchez, Mingjie Li, Cathy Wang, Cydney M. Nichols, Jennifer Li, Haiming Chen and James R. Berenson
Clin Cancer Res July 15 2012 (18) (14) 3856-3867; DOI: 10.1158/1078-0432.CCR-11-3130
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Clinical Cancer Research
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