X. Xu et al., ADENOVIRUS-MEDIATED INTERFERON-GAMMA TRANSFER INHIBITS GROWTH OF TRANSPLANTED HTLV-I TAX TUMORS IN MICE, Human gene therapy, 7(4), 1996, pp. 471-477
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.