The role of interleukin-2 in combination adenovirus gene therapy for head and neck cancer

Molecular Endocrinology
B W O'MalleyL Duan

Abstract

Interleukin-2 (IL-2) gene therapy alone and in combination with the herpes thymidine kinase gene (tk) was used to evaluate immunological responses and antitumor effects in head and neck cancer. Established floor of mouth squamous cell carcinomas in C3H/HeJ mice were directly injected with recombinant adenoviral vectors carrying both therapeutic and control genes. One week after adenoviral gene transfer, only the animals treated with combination IL-2+tk or tk alone demonstrated significant tumor regression. Residual tumors were harvested for microscopic evaluation and immunohistochemistry staining, which revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL-2. To evaluate the systemic immune effects of IL-2, animals treated with single or combination gene therapy received a second site challenge with parental tumor cells or a heterologous but syngeneic sarcoma cell line. Mice treated with combination IL-2 and tk demonstrated a protective systemic immunity specific to the parental tumor cell line, whereas no systemic immune response was evident in mice receiving IL-2 alone. In a separate experiment, a range of concentrations of the adenovirus IL-2 vector were used to treat established tumors...Continue Reading

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Citations

Mar 25, 1999·The Laryngoscope·B W O'MalleyD M Pardoll
Apr 20, 2004·Cancer Immunology, Immunotherapy : CII·Thomas K HoffmannTheresa L Whiteside
Dec 21, 2000·Current Oncology Reports·G L Clayman, L Dreiling
May 23, 2001·The Laryngoscope·D LiB W O'Malley
Nov 24, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·J Nemunaitis, J O'Brien

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