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


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.


CONCLUSIONS
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.
University of Alabama at Birmingham, Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, 1670 University Boulevard, Volker Hall G082, Birmingham, AL 35233, USA.
Larissa
L
Sweeny
Yolanda E
YE
Hartman
Kurt R
KR
Zinn
James R
JR
Prudent
David J
DJ
Marshall
Mohammed S
MS
Shekhani
Eben L
EL
Rosenthal
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D051926:Basigin / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005240:Feasibility Studies; D005260:Female; D000922:Immunotoxins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D051926:Basigin; D000254:Sodium-Potassium-Exchanging ATPase
Aerodigestive squamous cell carcinoma; CD147; Extracellular drug conjugate; HNSCC; Head and neck; head and neck squamous cell carcinoma