A DNA Vaccine against ERBB2 Impairs Chemical Carcinogenesis in Random-Bred Hamsters

Abstract

Vaccines against oncoantigens halt early neoplastic lesions in several cancer-prone, genetically engineered mouse models, whereas their ability to prevent chemical carcinogenesis has not been explored. This is a significant issue, as exposure to chemical mutagens is responsible for a substantial percentage of cancers worldwide. Here, we show that the archetypal oncoantigen ERBB2 is transiently overexpressed in Syrian hamsters during the early stages of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis. Repeated DNA vaccinations against ERBB2 significantly reduce the number, size, and severity of oral lesions in a manner directly proportional to the anti-ERBB2 antibody response. These results support the prospects of vaccines as a fresh strategy in the management of individuals at risk for exposure to defined carcinogenic agents. Cancer Prev Res; 4(7); 994-1001. Ó2011 AACR.

ErbB2 Receptor Over-Expression Improves Post-Traumatic Peripheral Nerve Regeneration in Adult Mice

“…This receptor is involved in the signal transduction pathways leading to physiologic processes, such as embryogenesis, cell proliferation, and apoptosis [11] and in regenerative processes concerning nerve [12], heart [13], pancreas [14]. However, its deregulation can drive cancer development and progression in some histotypes; from this point of view ErbB2 is an oncogene having a role as a negative prognostic marker [15], [16], [17] and as a target for antineoplastic therapy [18], [19], [20], [21]. No ErbB2 ligands have been identified yet.…”

The Hamster Model of Sequential Oral Carcinogenesis: An Update

“…For example, this hamster model of sequential carcinogenesis was used to evaluate the antitumor potential of rosmarinic acid, lyophilized strawberries, black raspberries and withaferin A in DMBAinduced hamster buccal pouch carcinogenesis based on the expression of basic genes related to tumor development (27)(28)(29)(30). Apart from these compounds, DNA vaccines against ERBB2 and the use of virosomes encapsulated with chlorin e6 and tagged anti-EGFR antibody were applied for the purpose of improving targeting ability against oral squamous cell carcinoma (31,32). For this purpose, they induced carcinogenesis in the hamster and classified different histological types, such as normal epithelium, low-grade (mild) dysplasia, high-grade (severe) dysplasia, and carcinoma in situ.…”

Vaccines for tumor prevention: a pipe dream?

“…Going toward a primary prevention, persons exposed to carcinogens for recreational (tobacco, alcohol), occupational (asbestos, radiations), or medical (cancer survivors) reasons can be considered. [43]. Finally, there are several persons at specific risk of cancer who could benefit from anti-cancer vaccines: individuals carrying genetic alterations that increase the risk of cancer, such as BRCA1/2 families.…”

“…[24,36,38]. Characterization of oncoantigens overexpressed during early stages of chemically induced pre-neoplastic lesions may allow the formulation of vaccines able to trigger a specific and persistent immune memory to be exploited as a fresh strategy for the management of individuals at a high risk for cancer following exposure to a specific carcinogenic agent, for whom no active therapeutic option exists at present [43].…”