Abstract

Effective prevention of human cancer with vaccines against viruses, such as HBV and HPV, raises the question whether also non-virus related tumors could be prevented with immunological means. Studies in HER-2-transgenic mice showed that powerful anti-HER-2 vaccines, could almost completely prevent the onset of mammary carcinoma. Protective immune responses were orchestrated by T cells and their cytokines, and effected by antibodies against HER-2 gene product p185. Analogous findings were reported in a variety of other cancer immunoprevention systems, thus leading to the definition of oncoantigens, optimal target antigens that are causally involved in carcinogenesis and cancer progression. Prophylactic HER-2 vaccines were also effective in preventing metastasis outgrowth, indicating that concepts and approaches developed for cancer immunoprevention could prove fruitful in cancer immunotherapy as well. The availability of cancer-prone mice carrying a human HER-2 transgene is now fostering the design of novel vaccines against human p185. A further bridge toward human cancer was recently provided by novel immunodeficient models, like Rag2−/−;Il2rg−/− mice, which are permissive for metastatic spread of human HER-2+ cancer cells and can be engrafted with a functional human immune system, allowing for the first time the study of vaccines against oncoantigens to elicit human immune responses against human cancer cells in vivo.

Highlights

  • Effective prevention of human cancer with vaccines against viruses, such as HBV and HPV, raises the question whether non-virus related tumors could be prevented with immunological means

  • Some years ago we found that BALB/c Rag2−/−;Il2rg−/− (BRG) mice are superior to nude mice for studies of metastatic dissemination of human sarcomas (Nanni et al, 2010), we compared the metastatic capacity of human HER-2+ breast cancer cell lines MDA-MB-453 and BT-474 in nude and in BRG mice (Nanni et al, 2012)

  • Our results in BRG mice clearly demonstrate that, in the case of HER-2+ carcinomas, the major obstacle to metastatic spread was the residual immune response of nude mice, in particular natural killer (NK) activity, and that the full metastatic potential of human cancer can be expressed in BRG mice

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Summary

Introduction

Effective prevention of human cancer with vaccines against viruses, such as HBV and HPV, raises the question whether non-virus related tumors could be prevented with immunological means. CANCER IMMUNOPREVENTION The immune system actively prevents tumor onset, as is clearly demonstrated by the huge increase in cancer development in genetically modified immunodeficient mice.

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