Ys. Haviv et al., Heat shock and heat shock protein 70i enhance the oncolytic effect of replicative adenovirus, CANCER RES, 61(23), 2001, pp. 8361-8365
Replication-competent viruses are currently being evaluated for their cance
r cell-killing properties. These vectors are designed to induce tumor regre
ssion after selective viral propagation within the tumor. However, replicat
ion-competent viruses have not resulted heretofore in complete tumor eradic
ation in the clinical setting. Recently, heat shock has been reported to pa
rtially alleviate replication restriction on an avian adenovirus (Ad) in a
human lung cancer cell line. Therefore, we hypothesized that beat shock and
overexpression of heat shock protein (lisp) would support the oncolytic ef
fect of a replication-competent human Ad. To this end, we tested the oncoly
tic and burst kinetics of a replication-competent Ad after exposure to heat
shock or to inducible lisp 70 overexpression by a replication-deficient Ad
(Adhsp 70i). Heat-shock resulted in augmentation of Ad burst and oncolysis
while decreasing total intracellular Ad DNA. Overexpression of lisp 70i al
so enhanced Ad-mediated oncolysis but did not decrease intracellular Ad DNA
levels. We conclude that heat shock and Adhsp 70i enhance the Ad cell-kill
ing potential via distinct mechanisms. A potential therapeutic implication
would be the use of local hyperthermia to augment oncolysis by increasing t
he burst of replication-competent Ad. The role of lisp in Ad-mediated oncol
ysis should be additionally explored.