Replication-Competent Herpes Simplex Virus Vector G207 and Cisplatin Combination Therapy for Head and Neck Squamous Cell Carcinoma

Abstract

Replication-competent virus vectors are attractive therapeutic agents for cancer. G207, a second-generation, multimutated herpes simplex virus type 1 (HSV-1), is one such vector that is safe in primates and efficacious against human tumors in athymic mice. Squamous cell carcinoma is the most frequently encountered malignancy of the head and neck, and the chemotherapeutic agent cisplatin is a standard treatment for recurrent head and neck cancer. In this study we examine the therapeutic potential of G207, alone and in combination with cisplatin, against squamous cell carcinoma. Human squamous cell carcinoma cell lines are sensitive to G207 replication and cytotoxicity in vitro at a multiplicity of infection of 0.01, including cisplatin sensitive (UMSCC-22A), moderately sensitive (UMSCC-38), and weakly sensitive (SQ20B) cell lines. Cisplatin did not inhibit the cytopathic effect of G207. G207 inhibited the growth of established subcutaneous head and neck tumors in athymic mice. The therapeutic effects of cisplatin and G207 in vivo were independent. However, in cisplatin-sensitive tumors (UMSCC-38), combination therapy resulted in 100% cures in contrast to 42% with G207 or 14% with cisplatin alone. We conclude that G207 should be considered for the treatment of head and neck cancer and that combination with chemotherapeutic agents may improve efficacy.

Keywords

• herpes simplex virus
• head and neck cancer
• squamous cell carcinoma
• cisplatin
• gene therapy