IL-2 gene therapy plus radiation generates potent antitumor response

Combining non-viral interleukin 2 gene therapy with external-beam radiation in a murine model leads to more extensive tumor cell apoptosis than is observed with either modality alone, study findings suggest.

Researchers examined this combined approach in an orthotopic murine model of head and neck squamous cell carcinoma based on previous reports showing efficacy in an animal model of renal adenocarcinoma. They report their findings in the Archives of Otolaryngology Head and Neck Surgery for June.Dr. Bert W. O’Malley, of the University of Maryland School of Medicine in Baltimore, and researchers there and at Valentis Inc., in The Woodlands, Texas, injected tumors with plasmids containing the expression cassette for murine interleukin-2 (mIL-2) on days 5 and 9 after tumors were established in the palates of mice. External-beam radiation therapy (XRT) was delivered on day 6.When they examined tumors on day 13, the researchers found increased expression of mIL-2 and murine interferon-gamma, and enhanced cytotoxic T lymphocyte (CTL) activity, after gene therapy. Combination treatment with mIL-2 and XRT resulted in significantly smaller tumors, and more apoptotic cells, compared with those achieved by either treatment alone. However, addition of XRT did not increase the immune response, suggesting that “the antitumor effects of combination mIL-2/XRT occur through parallel mechanisms,” Dr. O’Malley’s team writes. Therefore, they recommend further optimizing the treatment in animal models, and evaluating the combination of mIL-2 gene therapy and XRT with surgery or chemotherapy “in a classic adjuvant strategy.” Furthermore, Dr. O’Malley and his associates write, “this novel strategy warrants consideration in human clinical trials for head and neck cancer.”(Source: Arch Otolaryngol Head Neck Surg 2003;129:618-622: Reuters Health: 23rd June 2003: Oncolink)