Reovirus salvage of squamous cell cancer-contaminated wounds

• Published in: Journal of otolaryngology Vol. 34; no. 1; p. 32
• Main Authors: Brookes, James T, Seikaly, Hadi, Lim, Thomas, Wong, Kevin K, Harris, Jeffery R, Moore, Ron B
• Format: Journal Article
• Language: English
• Published: Canada 01.02.2005
• Subjects: Animals; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - virology; Cell Line, Tumor; Genes, ras - genetics; Hypopharyngeal Neoplasms - genetics; Hypopharyngeal Neoplasms - virology; In Vitro Techniques; Mice; Reoviridae Infections - genetics; Reoviridae Infections - virology; Salvage Therapy - methods; Therapeutic Irrigation
• ISSN: 0381-6605
• DOI: 10.2310/7070.2005.03059

To assess the susceptibility of human squamous cell carcinoma to reovirus infection in vitro and in vivo using a murine model of cancer-contaminated wounds. The University of Michigan squamous carcinoma 22B cell line was cultured and inoculated with reovirus in vitro. The effect of the reovirus was assessed with microscopy and a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. We used the previously established cancer-contaminated wound SCID mouse model to test saline and reovirus irrigation in vivo. Fifty-five mice were used; 15 were controls, 20 had immediate irrigation, and 20 had delayed irrigation. Surgical sites were assessed for palpable tumour biweekly. The microscopy and MTT assay both showed evidence of reovirus-mediated squamous cancer cell lysis. The control mice grew palpable tumours in 80% of the wounds. Immediate irrigation with saline delayed the onset of palpable tumour and demonstrated a persistent reduction in the rate of development of palpable tumours (p = .004 compared with controls). This effect disappeared when the saline irrigation was delayed, resulting in a tumour development rate that was not significantly different from that of the control. Wounds that were irrigated with reovirus, both immediately and delayed, did not produce palpable tumour (p < .0005 when compared with controls). (1) The University of Michigan squamous cell carcinoma 22B cell line is susceptible to reovirus in vitro. (2) Immediate irrigation with saline resulted in a significant delay in clinically evident tumour growth and a reduction in the rate of tumour development in the SCID mouse model. (3) The reovirus irrigation resulted in a significant reduction of tumour development in both the immediate and delayed groups in the SCID mouse model. (4) The efficacy of the reovirus irrigation in the delayed group suggests that the major mechanism of action is through a selective and specific targeting of implanted cancer cells.