PMID- 8800741 OWN - NLM STAT- MEDLINE DCOM- 19961001 LR - 20181130 IS - 1043-0342 (Print) IS - 1043-0342 (Linking) VI - 7 IP - 4 DP - 1996 Mar 1 TI - Adenovirus-mediated interferon-gamma transfer inhibits growth of transplanted HTLV-1 Tax tumors in mice. PG - 471-7 AB - Human T cell leukemia virus type 1 (HTLV-1) causes adult T cell leukemia (ATL), and the virus-encoded trans-activator, Tax, plays an important role in T cell transformation. In the HTLV-1 long terminal repeat (LTR)-Tax transgenic mouse model, Tax expression causes fibroblastic tumors. A tumor-derived cell line (B line) obtained from an explant of a Tax-transformed tumor, was established. This line expresses high levels of many cytokines as a consequence of Tax activation. However, the tumors are not immunogenic when transplanted into syngeneic mice. Because B line cells do not express the immunogenic cytokine interferon-gamma (IFN-gamma), a replication-defective adenoviral vector was used to deliver the IFN-gamma gene to tumor cells. The recombinant IFN-gamma adenovirus (IFN-gamma/Ad) can efficiently infect B line cells, resulting in high levels of IFN-gamma expression and secretion. Local secretion of IFN-gamma from B line cells caused both CD(4+)- and CD(8+)-positive T cell infiltration, and completely inhibited local tumor development in transplanted mice. Immunization with these cells significantly delayed tumor development after subsequent challenges of parental tumor cells. Expression of IFN-gamma in B cells also partially inhibited the highly expressed immune suppressive cytokine, transforming growth factor-beta 1 (TGF-beta 1). This system provides us with a valuable tumor immune therapy model to evaluate the effects of cytokines in induction or inhibition of specific antitumor immunity. FAU - Xu, X AU - Xu X AD - Department of Molecular and Experimental Medicine, Scripps Research Institue, La Jolla, CA 92037, USA. FAU - Dai, Y AU - Dai Y FAU - Heidenreich, O AU - Heidenreich O FAU - Nerenberg, M I AU - Nerenberg MI LA - eng GR - CA50234/CA/NCI NIH HHS/United States GR - NS12428/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Hum Gene Ther JT - Human gene therapy JID - 9008950 RN - 0 (Gene Products, tax) RN - 0 (Transforming Growth Factor beta) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adenoviruses, Human/*genetics MH - Animals MH - B-Lymphocytes/cytology MH - Down-Regulation MH - Fibrosarcoma/*therapy MH - Gene Expression MH - Gene Products, tax/genetics/metabolism MH - Gene Transfer Techniques MH - *Genetic Therapy MH - Genetic Vectors MH - *Human T-lymphotropic virus 1 MH - Humans MH - Interferon-gamma/*genetics/metabolism/therapeutic use MH - Mice MH - Mice, Inbred C57BL MH - Neoplasm Transplantation MH - Transforming Growth Factor beta/genetics/metabolism MH - Tumor Cells, Cultured MH - Vaccination EDAT- 1996/03/01 00:00 MHDA- 1996/03/01 00:01 CRDT- 1996/03/01 00:00 PHST- 1996/03/01 00:00 [pubmed] PHST- 1996/03/01 00:01 [medline] PHST- 1996/03/01 00:00 [entrez] AID - 10.1089/hum.1996.7.4-471 [doi] PST - ppublish SO - Hum Gene Ther. 1996 Mar 1;7(4):471-7. doi: 10.1089/hum.1996.7.4-471.