Immunization with xenogeneic
DNA is a promising
cancer treatment to overcome tolerance to
self-antigens.
Heat shock protein 70 (HSP70) is over-expressed in various kinds of
tumors and is believed to be involved in
tumor progression. This study tested a xenogeneic chicken HSP70 (chHSP70)
DNA vaccine in an experimental canine
transmissible venereal tumor (CTVT) model. Three vaccination strategies were compared: the first (PE) was designed to evaluate the prophylactic efficacy of chHSP70
DNA vaccination by delivering the
vaccine before
tumor inoculation in a prime boost setting, the second (T) was designed to evaluate the therapeutic efficacy of the same prime boost
vaccine by vaccinating the dogs after
tumor inoculation; the third (PT) was similar to the first strategy (PE), with the exception that the electroporation booster injection was replaced with a transdermal needle-free injection.
Tumor growth was notably inhibited only in the PE dogs, in which the vaccination program triggered
tumor regression significantly sooner than in control dogs (NT). The CD4(+) subpopulation of tumor-infiltrating lymphocytes and canine HSP70 (caHSP70)-specific IFN-γ-secreting lymphocytes were significantly increased during
tumor regression in the PE dogs as compared to control dogs, demonstrating that specific tolerance to caHSP70 has been overcome. In contrast, no benefit of the therapeutic strategy (T) could be noticed and the (PT) strategy only led to partial control of
tumor growth. In summary, antitumor prophylactic activity was demonstrated using the chHSP70
DNA vaccine including a boost via electroporation. Our data stressed the importance of
DNA electroporation as a booster to get the full benefit of
DNA vaccination but also of
cancer immunotherapy initiation as early as possible. Xenogeneic chHSP70
DNA vaccination including an electroporation boost is a potential
vaccine to HSP70-expressing
tumors, although further research is still required to better understand true clinical potential.