Active specific immunotherapy against occult brain metastasis.
We determined whether lyophilized High Five (H5) insect cells engineered to produce IFN-beta (H5BVIFN-beta) could induce systemic immunity against occult brain metastases. C3H/HeN mice were injected s.c. with syngeneic UV-2237M fibrosarcoma or K-1735M2 melanoma cells. Intralesional injection of 2 x 10(6) lyophilized H5BVIFN-beta cells produced complete regression of the s.c. tumors. Six weeks later, UV-2237M fibrosarcoma cells or K-1735M2 melanoma cells were injected into the internal carotid artery of naive or treated mice. UV-2237M brain metastases developed in naive mice or mice cured of K-1735M2 tumors but not in mice cured of UV-2237M tumors. Similarly, K-1735M2 brain metastases developed in naive mice or mice cured of UV-2237M fibrosarcomas but not in mice cured of K-1735M2 melanoma. In the next set of studies, mice were injected s.c. with UV-2237M fibrosarcoma cells. On day 7, UV-2237M fibrosarcoma cells or K-1735M2 cells were implanted into the internal carotid artery, and on day 10, the s.c. tumors were injected with lyophilized H5BVIFN-beta. Both the s.c. tumors and the occult brain metastases produced from carotid injections were eradicated in a tumor-specific manner. The regression of the brain metastases was abrogated by depletion of CD4(+) or CD8(+) cells from immunized mice. These results demonstrate that specific systemic immunity can be induced by lyophilized H5BVIFN-beta and that the resultant immune response can eliminate established brain metastasis.
Lu
Weixin
W
Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
Su
Jindong
J
Kim
Lee Su
LS
Bucana
Corazon D
CD
Donawho
Cherrie
C
He
Junqing
J
Fidler
Isaiah J
IJ
Dong
Zhongyun
Z
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001932:Brain Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005354:Fibrosarcoma / Q000276:immunology / Q000556:secondary / Q000628:therapy; D005822:Genetic Vectors / Q000235:genetics; D016233:Immunotherapy, Active / Q000379:methods*; D007313:Insecta / Q000821:virology; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology
D016899:Interferon-beta