ADENOVIRUS-MEDIATED INTERFERON-GAMMA TRANSFER INHIBITS GROWTH OF TRANSPLANTED HTLV-I TAX TUMORS IN MICE

Human T cell leukemia virus type I (HTLV-1) causes adult T cell leukem ia (ATL), and the virus-encoded trans-activator, Tax, plays an importa nt role in T cell transformation. In the HTLV-1 long terminal repeat ( LTR)-Tax transgenic mouse model, Tax expression causes fibroblastic tu mors. A tumor-derived cell line (B line) obtained from an explant of a Tax-transformed tumor, was established. This line expresses high leve ls of many cytokines as a consequence of Tax activation. However, the tumors are nor immunogenic when transplanted into syngeneic mice. Beca use B line cells do not express the immunogenic cytokine interferon-ga mma (IFN-gamma), a replication-defective adenoviral vector was used to deliver the IFN-gamma gene to tumor cells. The recombinant IEN-gamma adenovirus (IFN-gamma/Ad) can efficiently infect B line cells, resulti ng in high levels of IFN-gamma expression and secretion. Local secreti on of IFN-gamma from B line cells caused both CD4(+)- and CD8(+)-posit ive T cell infiltration, and completely inhibited local tumor developm ent in transplanted mice. Immunization with these cells significantly delayed tumor development after subsequent challenges of parental tumo r cells. Expression of IFN-gamma in B cells also partially inhibited t he highly expressed immune suppressive cytokine, transforming growth f actor-beta(1) (TGF-beta(1)). This system provides us with a valuable t umor immune therapy model to evaluate the effects of cytokines in indu ction or inhibition of specific antitumor immunity.