HNSCC continues to be the sixth leading cause of cancer. Tumor recurrences affect 40%-50% of HNSCC patients owing to field cancerization. Currently available therapeutic modalities for advanced HNSCC, such as surgery with radiotherapy or chemotherapy, are of limited efficacy, and often result in severe cosmetic deformity, significant functional deficits in speech and swallowing, local radionecrosis, fibrosis, chronic pain, muscle atrophy, and xerostomia. Over the past 30 years, overall survival has not significantly improved, thus, new therapeutic approaches are needed for HNSCC. Recently, engineered and naturally oncolytic viruses have demonstrable local and systemic efficacy in many cancer types. Targeted oncolytic viruses may be a treatment that can improve morbidity and mortality of HNSCC.
Adenoviruses, double-stranded DNA viruses, are a group of many viruses that are responsible for transient upper respiratory infection and are uniquely suited for the treatment of HNSCC. They have been engineered to become conditionally replicative adenoviruses.
ONYX-015 is an engineered adenovirus with the deletion of E1B-55K gene, and it can replicate in and lyse p53-deficient cancer cells. Due to the upregulation of the CD46 receptor, ONYX-015 was genetically modified to create an Ad5/35 chimeric virus by substituting the Ad5 fiber or penton for the Ad35 fiber to enhance potency. This virus has shown good tumor selectivity and safety. A phase II clinical study with ONYX-015 injection in 24 head and neck cancer patients have shown highly selective tissue destruction with significant tumor regression in 21% of evaluable patients, with no toxicity to injected normal peritumoral tissues.
OBP-301, a telomerase-specific replication-selective adenovirus, was also able to overcome radio-resistance of head and neck cancer in an orthotopic nude mouse model. Both in vitro and in vivo, infection with OBP-301 was found to enhance the antitumor efficacy of radiation by increasing apoptosis induction. Moreover, OBP-301 either alone or in combination with paclitaxel or cisplatin has been found to exert significant antitumor effects on HNSCC cells both in vitro and in vivo.
HF10 is a spontaneously occurring mutant form of the HSV-1 virus lacking the UL56 protein, which is important for cytoplasmic transport and release of virions. HF10 has been evaluated its anticancer efficacy in a variety of animal models. Intratumoral injection of HF10 into subcutaneous nodules in patients with HNSCC have been reported. HF10 can efficiently infect human HNSCC cells and cause extensive tumor cell death without any significant adverse effects, suggesting that HF10 represents a promising therapy for HNSCC in humans. A preliminary study of toxicity and efficacy in two patients with HNSCC was performed to assess the therapeutic potential of HF10 in human HNSCC. A metastatic skin nodule of each patient was injected with HF10. The results indicated that HF10 spread well in the tumor nodules, and caused cell death in a considerable population of tumor cells without any significant adverse effect.
HSV1716 is a selectively replicating oncolytic HSV type I virus which replicates and lyses actively dividing cells but not normal or terminally differentiated cells. This virus lacks both copies of the RL1 gene, which encodes the virulence protein ICP 34.5. In vitro and in vivo studies have shown selective replication and cytolysis in a variety of tumor types. HSV1716 alone and combined with cisplatin was efficacious in destroying HNSCC cells. Combination treatment with HSV1716 and cisplatin gave additive efficacy. These results indicate that HSV1716 in combination with cisplatin could be of therapeutic value in HNSCC.
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