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Replication-competent herpes simplex virus vector G207 and cisplatin combination therapy for head and neck squamous
A Chahlavi1, T Todo, R L Martuza
1Department of Neurosurgery, Georgetown University Medical Center, Washington, DC 20007, USA.
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.
Insights
This study shows that G207, a herpes simplex virus type 1 (HSV-1) vector, effectively treats head and neck squamous cell carcinoma. Combining G207 with cisplatin significantly improves cure rates in cisplatin-sensitive tumors.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Herpes simplex virus (HSV) vectors
Background:
- Replication-competent virus vectors show promise for cancer therapy.
- G207, a second-generation HSV-1 vector, is safe and effective against human tumors.
- Squamous cell carcinoma is a common head and neck cancer treated with cisplatin.
Purpose of the Study:
- To evaluate the therapeutic potential of G207 alone and with cisplatin against squamous cell carcinoma.
- To assess G207's efficacy in human squamous cell carcinoma cell lines and in mouse models.
- To determine if combination therapy enhances anti-cancer effects.
Main Methods:
- In vitro testing of G207 replication and cytotoxicity on human squamous cell carcinoma cell lines.
- In vivo studies using G207 and cisplatin in athymic mouse models with subcutaneous head and neck tumors.
- Evaluation of combination therapy effects on tumor growth and cure rates.
Main Results:
- Human squamous cell carcinoma cell lines were sensitive to G207 replication and cytotoxicity in vitro.
- G207 inhibited the growth of established head and neck tumors in mice.
- Combination therapy of G207 and cisplatin achieved 100% cures in cisplatin-sensitive tumors, compared to 42% for G207 alone and 14% for cisplatin alone.
Conclusions:
- G207 demonstrates therapeutic potential for head and neck cancer treatment.
- Combination therapy with G207 and cisplatin may significantly improve treatment efficacy, especially in cisplatin-sensitive tumors.