Her-2/neu Transgenic Mice for Evaluation of Immune and Antitumor Responses Against Self-Tumor Antigens in the Young and the Old

Abstract

The impact of aging on T-cell tolerance has yet to be elucidated. More importantly cancer vaccines that will be effective both in the young and the old have yet to be developed. As a result, there is a need for relevant tumor models which include aspects of self-tolerance and development of spontaneous tumors in the aged. Such models are critical for the development and optimization of specific cancerrelated immunotherapeutic strategies for the elderly. Although the majority of studies augmenting immune responses against a self-antigen like the Her-2/neu have used young Her-2/neu transgenic mouse models and put a lot of effort into aspects such as increasing the immunogenicity, very little attention has been paid to the immune competence of the aging population. Based on the Her-2/neu transgenic mice, our group has developed a mouse model (HLA-A2.1/Kb mice crossed with the FVBHer- 2/neu mice) where self-tolerance, spontaneous tumor progression and aging are present simultaneously. The immunological aspects of the A2xneu mice closely reflect those of cancer patients whose immune systems are not fully competent to reject their tumors. Models like this are critical as they may provide data that closely predict the clinical outcomes and will help to customize immunotherapeutic strategies that would be effective for the treatment of tumors in both the young and the old. In this chapter, we will focus on the Her-2/neu transgenic mouse model for the evaluation of immune and antitumor responses against a self-tumor antigen in both the young and the old.