Treatment of a human breast cancer xenograft with an adenovirus vector containing an interferon gene results in rapid regression due to viral oncolysis and gene therapy.
Treatment of a human breast cancer cell line (MDA-MB-435) in nude mice with a recombinant adenovirus containing the human interferon (IFN) consensus gene, IFN-con1 (ad5/IFN), resulted in tumor regression in 100% of the animals. Tumor regression occurred when virus was injected either within 24 hr of tumor cell implantation or with established tumors. However, regression of the tumor was also observed in controls in which either the wild-type virus or a recombinant virus containing the luciferase gene was used, although tumor growth was not completely suppressed. Tumor regression was accompanied by a decrease in p53 expression. Two other tumors, the human myelogenous leukemic cell line K562 and the hamster melanoma tumor RPMI 1846, also responded to treatment but only with ad5/IFN. In the case of K562 tumors, there was complete regression of the tumor, and tumors derived from RPMI 1846 showed partial regression. We propose that the complete regression of the breast cancer with the recombinant virus ad5/IFN was the result of two events: viral oncolysis in which tumor cells are being selectively lysed by the replication-competent virus and the enhanced effect of expression of the IFN-con1 gene. K562 and RPMI 1846 tumors regressed only as a result of IFN gene therapy. This was confirmed by in vitro analysis. Our results indicate that a combination of viral oncolysis with a virus of low pathogenicity, itself resistant to the effects of IFN and IFN gene therapy, might be a fruitful approach to the treatment of a variety of different tumors, in particular breast cancers.
Zhang
J F
JF
Department of Biology, Indiana University, Bloomington 47405, USA.
Hu
C
C
Geng
Y
Y
Selm
J
J
Klein
S B
SB
Orazi
A
A
Taylor
M W
MW
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000628:therapy; D008156:Luciferases / Q000096:biosynthesis; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D016159:Tumor Suppressor Protein p53; D007372:Interferons; D008156:Luciferases