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Scott E. Strome, MD; John C. Krauss, MD; Mark J. Cameron, MS; Kristina Forslund; Suyu Shu, PhD; Alfred E. Chang, MD

Arch Otolaryngol Head Neck Surg. 1993;119(12):1289-1295.

Abstract
Objective
The genetic modification of tumors offers an approach to modulate the host immune response to relatively weak native tumor antigens. We examined the immunobiologic effects of various cytokine genes transferred into the poorly immunogenic B16-BL6 murine melanoma.

Design
Retroviral expression vectors containing cDNAs for interleukin 2, interleukin 4, interferon gamma, or a neomycin-resistant control were electroporated into a B16-BL6 tumor clone. Selected transfected clones were examined for in vitro cytokine secretion and in vivo tumorigenicity.

Results
When cells from individual clones were injected intradermally into syngeneic mice, the interleukin 4—secreting clone grew significantly slower than did the neomycin-resistant transfected control, while the growth of the interleukin 2– and interferon gamma—expressing clones was not affected. Despite minimal cytokine secretion by interferon gamma—transfected cells, these cells expressed upregulated major histocompatibility class I antigen and were more susceptible to lysis by allosensitized cytotoxic T lymphocytes compared with parental or neomycin-resistant transfected tumor targets.

Conclusions
We observed diverse immunobiologic effects associated with cytokine gene transfer into the B16-BL6 melanoma. Interleukin 4 transfection of tumor resulted in decreased in vivo tumorigenicity that may be related to a host immune response. Further studies to evaluate the host T-cell response to these gene-modified tumors are being investigated.

(Arch Otolaryngol Head Neck Surg. 1993;119:1289-1295)

Author Affiliations
From the Department of Otolaryngology (Dr Strome), Division of Hematology and Oncology, Department of Internal Medicine (Dr Krauss and Ms Forslund), and the Division of Surgical Oncology, Department of Surgery (Mr Cameron and Drs Shu and Chang), University of Michigan, Ann Arbor.

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