Specific immunotherapy against occult cancer metastases.
We investigated the efficacy of a preparation containing High Five (H5) insect cells infected with recombinant baculovirus encoding the murine interferon-beta gene (H5BVIFN-beta) against established primary tumors and occult lung metastases. Injection of live or lyophilized H5BVIFN-beta into established subcutaneous tumors of the highly metastatic murine UV-2237m fibrosarcoma or K-1735M2 melanoma in syngeneic mice eradicated both primary tumors and preexisting lung metastases. The therapeutic effects of H5BVIFN-beta were not observed in nude mice and were diminished in syngeneic mice depleted of CD4(+) and CD8(+) T cells. Immunohistochemical staining showed that tumors injected with H5BVIFN-beta were densely infiltrated by CD4(+) and CD8(+) T cells in mice with normal CD4/CD8 complement. These data demonstrate that, unlike most immunologic approaches in which prophylaxis can be achieved but eradication of established tumor is rare, lyophilized preparations of H5BVIFN-beta can serve as a novel immunotherapy against both primary tumors and their occult metastases.
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Weixin
W
Lu
Zhongyun
Z
Dong
Cherrie
C
Donawho
Isaiah J
IJ
Fidler
D000818:Animals; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D007167:Immunotherapy; D007313:Insecta / Q000166:cytology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009382:Neoplasms, Unknown Primary / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D016899:Interferon-beta