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

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 (0.25–5.00 μg/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3–10 mg/kg), anti-CD147 monoclonal antibody, cisplatin (1 mg/kg) or radiation therapy (2 Gy/week) monotherapy or in combination. Results In vitro, treatment with minimal concentration of EDC22 (0.25 μg/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.

Emerging formats for next-generation antibody drug conjugates

“…A 24 PEG-repeating chain (around 95Å long) was used to 'tether' the payload in what's described as an extracellular drug conjugate (EDC). Against oral cancers activity, an anti-CD147 EDC was potent in vitro at < 1 µg/ml and tumour growth inhibition observed at 3 mg/kg [51].…”

“…Centrose have carried out the conjugation of a sugar-based drug capable of inhibiting the Na + -K + -ATPase function called bufadienolide aminoglycoside to a full tumour-specific IgG via hinge region disulphides [51]. A 24 PEG-repeating chain (around 95Å long) was used to 'tether' the payload in what's described as an extracellular drug conjugate (EDC).…”

Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection

“…Alternatively, a class of non-internalizing ADCs, referred to as extracellular drug conjugates (EDCs), is being developed. In the case of EDCs, drug release is not required as the payload acts on the cell surface while still attached to the antibody and interacts with a specific cell-surface antigen (9).…”

Prostate cancer relevant antigens and enzymes for targeted drug delivery

“…163 Moreover, the use of monoclonal antibody targeting CD147 for targeted delivery of small molecule drugs to CD147-overexpressing HNSCC (head and neck squamous cell carcinoma) cells showed significantly decreased cellular proliferation and cell viability. 164 …”