A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma

Oral Oncol. 2013 Oct;49(10):991-7. doi: 10.1016/j.oraloncology.2013.07.006. Epub 2013 Aug 3.

Abstract

Objectives: Despite advances in treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat with poor survival and high morbidity, necessitating a therapy with greater efficacy. EDC22 is an extracellular drug conjugate of the monoclonal antibody targeting CD147 (glycoprotein highly expressed on HNSCC cells) linked with a small drug molecule inhibitor of Na, K-ATPase. In this study, EDC22's potential as a treatment modality for HNSCC was performed.

Materials and methods: HNSCC cell lines (FADU, OSC-19, Cal27, SCC-1) were cultured in vitro and proliferation and cell viability were assessed following treatment with a range of concentrations of EDC22 (0.25-5.00μg/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3-10mg/kg), anti-CD147 monoclonal antibody, cisplatin (1mg/kg) or radiation therapy (2Gy/week) monotherapy or in combination.

Results: In vitro, treatment with minimal concentration of EDC22 (0.25μg/mL) significantly decreased cellular proliferation and cell viability (p<0.0001). In vivo, systemic treatment with EDC22 significantly decreased primary tumor growth rate in both an orthotopic mouse model (OSC-19) and a flank tumor mouse model (SCC-1) (p<0.05). In addition, EDC22 therapy resulted in a greater reduction in tumor growth in vivo compared to radiation monotherapy (p<0.05) and a similar reduction in tumor growth compared to cisplatin monotherapy. Combination therapy provided no significant further reduction in tumor growth relative to EDC22 monotherapy.

Conclusion: EDC22 is a potent inhibitor of HNSCC cell proliferation in vitro and in vivo, warranting further investigations of its clinical potential in the treatment of HNSCC.

Keywords: Aerodigestive squamous cell carcinoma; CD147; Extracellular drug conjugate; HNSCC; Head and neck; head and neck squamous cell carcinoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Basigin / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Feasibility Studies
  • Female
  • Immunotoxins / chemistry
  • Immunotoxins / pharmacology*
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Immunotoxins
  • Basigin
  • Sodium-Potassium-Exchanging ATPase