AN IMMUNE COMPETENT MOUSE TUMOR MODEL TO DEVELOP BREAST CANCER VACCINES FOR ELDERLY.
R. Sypniewska, L. Hoflack, L, C. Gravekamp*.
Cancer Therapy and Research Center, 14960 Omicron Drive, San Antonio, TX 78245.
The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. However, available mouse models do not permit to test novel cancer therapies on the same tumor in a young and old environment. Vaccine therapy is potentially less toxic than most of the currently used drug therapies and could, therefore, be especially valuable in the elderly population. For the development of cancer vaccines, immune competent mice with autologous tumors expressing tumor-associated antigens (TAA) is essential to activate tumor-specific cytotoxic T lymphocytes (CTL), and to destroy tumor cells. TAA, often exclusively expressed at the membrane of tumor cells are therefore particularly interesting for vaccine development. An additional problem is that elderly react less efficiently to vaccine therapies than young adults. This is probably due to T cell unresponsiveness, a phenomenon observed in cancer patients and elderly. One approach to activate tumor-specific CTL might be use of TAA-encoding DNA vaccines. The purpose of this study is to create a mouse tumor model that allows (1) developing and optimizing of a TAA-encoding DNA vaccine for the elderly with breast cancer, and (2) testing tumor immunological parameters in relation to aging. For the creation of this model a mouse tumor cell line 64pT (derived from an MMTV-infected Balb/C mouse) and 64pT-induced breast tumors were screened for the expression of mouse TAA that are homologous to human TAA. Expression of Smage was found in the 64pT tumor cell line and in 64pT-induced tumors by RT-PCR and southern blotting. Results were confirmed by DNA sequence analysis. Smage is homologous with the human TAA MAGE. This result allows the induction of Smage-expressing breast tumors at young and old age in immune competent mice by injection of the 64pT tumor cell line into normal Balb/C mice at young and old age. Subsequently, the Smage-specific RT-PCR fragments were cloned into an eukaryotic expression vector, and cloned products were characterized by DNA sequencing and western blotting. Smage protein (40.7 kDa) was detected in MCF-7 cells that were transfected with the created Smage-expressing vector. This Smage-enco
Key words:
elderly, cancer vaccines, tumor-associated antigens, mouse tumor models.
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