One of the main advantages of gene therapy over traditional therapy is the
potential to target the expression of therapeutic genes in desired cells or
tissues. To achieve targeted gene expression, we experimented with a new a
pproach based on the long-established phenomenon of the heat shock response
, ny using the green fluorescence protein as a reporter gene, it was demons
trated that expression of a heterologous gene with a heat shock protein 70
promoter could be elevated to 500-1000-fold over background by moderate hyp
erthermia (39 degrees C to 43 degrees C) in tissue cultured cells. The heat
-induced green fluorescence protein expression was first detectable at 3 h
after heating and reached a maximum at 18-24 h. The expression dropped back
to baseline within 72 h, In addition, when cells were infected with adenov
irus vectors containing the heat-inducible interleukin 12 or tumor necrosis
factor alpha genes and then heated (42 degrees C, 30 min), expression was
at least 13,600- or 6.8 x 10(5)-fold over background, respectively. Intrale
sion injection of the interleukin-12-carrying adenovirus vector in a mouse
melanoma tumor model caused significant tumor growth delay only with hypert
hermia treatment. Our results therefore support heat-induced gene expressio
n as a feasible approach for targeted cancer gene therapy.