Antibody-targeted chemotherapy for the treatment of melanoma

Wendy K. Nevala, Sarah A. Buhrow, Daniel J. Knauer, Joel M Reid, Elena A. Atanasova, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Antibody-directed chemotherapy (ADC) offers an advantage over conventional chemotherapy because it provides antibodydirected targeting, with resultant improvement in therapeutic efficacy and reduced toxicity. Despite extensive research, with notable exceptions, broad clinical application of ADC remains elusive; major hurdles include the instability of antibody-chemotherapy linkers and reduced tumor toxicity of the chemotherapy when bound to the antibody. To address these challenges, we have developed a platform technology that utilizes the nab-paclitaxel formulation of paclitaxel, Abraxane, in which hydrophobic paclitaxel is suspended in 130-nm albumin nanoparticles and thus made water-soluble. We have developed a method to noncovalently coat the Abraxane nanoparticle with recombinant mAbs (anti-VEGF, bevacizumab) and guide Abraxane delivery into tumors in a preclinical model of human A375 melanoma. Here, we define the binding characteristics of bevacizumab and Abraxane, demonstrate that the chemotherapy agent retains its cytotoxic effect, while the antibody maintains the ability to bind its ligand when the two are present in a single nanoparticle (AB160), and show that the nanoparticle yields improved antitumor efficacy in a preclinical human melanoma xenograft model. Further data suggest that numerous therapeutic monoclonal IgG1 antibodies may be utilized in this platform, which has implications for many solid and hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)3954-3964
Number of pages11
JournalCancer Research
Volume76
Issue number13
DOIs
StatePublished - Jul 1 2016

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Melanoma
Drug Therapy
Nanoparticles
Antibodies
Paclitaxel
Therapeutics
Hematologic Neoplasms
Heterografts
Vascular Endothelial Growth Factor A
Albumins
Neoplasms
Immunoglobulin G
Monoclonal Antibodies
Ligands
Technology
Albumin-Bound Paclitaxel
Water
Research
Bevacizumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Antibody-targeted chemotherapy for the treatment of melanoma. / Nevala, Wendy K.; Buhrow, Sarah A.; Knauer, Daniel J.; Reid, Joel M; Atanasova, Elena A.; Markovic, Svetomir Nenad.

In: Cancer Research, Vol. 76, No. 13, 01.07.2016, p. 3954-3964.

Research output: Contribution to journalArticle

Nevala, Wendy K. ; Buhrow, Sarah A. ; Knauer, Daniel J. ; Reid, Joel M ; Atanasova, Elena A. ; Markovic, Svetomir Nenad. / Antibody-targeted chemotherapy for the treatment of melanoma. In: Cancer Research. 2016 ; Vol. 76, No. 13. pp. 3954-3964.
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