Title

 

Authors

G. N. Berta¹, A. E. Sprio¹, P. Salamone¹, F. Di Scipio¹, G. Forni¹, F. Cavallo<sup>1

1</sup> Department of Department of Clinical and Biological Sciences, University of Turin 

 

Abstract

Immunoprevention of tumors connected with microbial infections is expected to decrease human tumor burden in the near future. Vaccines addressing tumor antigens with a causal role in the promotion of carcinogenesis unrelated to infections (oncoantigens) effectively halt the progression of early stages of neoplastic lesions in several genetically engineered cancer prone mice. The success of these anti-oncoantigen vaccines lies in their ability to target molecules delivering signals that play an essential role in driving the early stages of the progression of neoplastic lesions. Here, we evaluated whether a DNA vaccine targeting an archetypal oncoantigen (ERBB2) hampers the progression of canceron random-bred hamsters. This model provides one of the best defined and unambiguous systems of oral carcinogenesis and displays several features of human oral cancer. The present study shows that ERBB2 oncogene is transiently overexpressed during the early stages of oral carcinogenesis induced by 7,12-dimethylbenz[α]anthracene (DMBA). The number, size and severity of oral lesions are significantly reduced in ERBB2-immunized hamsters. The intensity of inhibition directly correlates with the titer of vaccine-elicited anti-ERBB2 antibodies. These findings show that vaccination against an oncoantigen transiently expressed during chemical carcinogenesis affords a significant protection. This suggests a new scenario in the management of individuals at high risk of cancer following exposure to a defined carcinogenic agent. Since vaccines against oncoantigens are especially effective in inhibiting early stages of cancer, characterization of those overexpressed during the initial phase of chemical carcinogenesis, along with the refinement of vaccines making them able to trigger innate and adaptive immune mechanisms, may form a fresh strategy in a preventive approach. In addition, the experimental evidence that an immune reaction to an oncoantigen expressed during chemical carcinogenesis impairs the progression of carcinogen-induced cancerous lesions may encourage the search for other ways (such as monoclonal antibodies or kinase inhibitors) to treat healthy individuals at risk, for which no active therapeutic option now exists.