Tailoring cancer vaccines to the elderly: the importance of suitable mouse models

The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. Vaccine therapy for cancer is potentially less toxic than chemotherapy or radiation and could, therefore, be especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. Activation of tumor-specific T cells by cancer vaccines might be an approach, especially suitable for elderly patients, to eradicate or to prevent recurrence of tumors after primary treatment. To tailor pre-clinical testing of vaccine therapies to the elderly, it is important to have mouse models in which tumors develop at equivalent time points in their life span, as in humans. Such models are currently not available. This progress report first summarizes the current knowledge of tumor-immunological parameters potentially involved in T cell unresponsiveness in relation to aging in mice and humans. Secondly, it reviews those cancer vaccines that are known for their potential to induce tumor-specific T cell responses. Thirdly, it discusses the usefulness of currently available mouse models for pre-clinical testing of cancer vaccines applicable to the elderly population. Finally, experimental approaches are proposed, as to how to develop mouse models that allow the induction of specific tumors at will at different ages, expressing tumor-specific antigens in an 'immune competent' environment. These mouse models may teach us how to overcome immune deficits in the elderly, thereby facilitating the development of effective and safe cancer vaccines. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.