The long term goal of this study is to determine if and how neoplastic progression can be interrupted by immunization with monoclonal anti- idiotypic (Id) antibodies (MAID) that resemble the antigenic structures on preneoplastic or neoplastic mammary lesions. Mouse mammary tumor virus (MMTV) associated gp52 is the model """"""""tumor-associated antigen."""""""" The effects of MAID immunization are determined in MMTV-free BALB/c mice and in syngeneic BALB/C cfC3H mice which are neonatally-infected with MMTV. Our experimental results indicate that immunization with MAID can induce both protective and suppressive immunity. In MMTV-free BALB/c mice, the protective immunity dominates and tumor growth is inhibited, whereas in MMTV-tolerant BALB/cfC3H mice, MAID may reinforce the existing suppressive mechanism because tumor growth is accelerated. The tumor enhancing effect of MAID in BALB/cfC3H mice is eliminated by 140 mg/kg of cyclophosphamide given one day after or 2 weeks before MAID immunization. BALB/c mice represent animals free of the cancer causing agent and MAID immunization of these mice provides a model for cancer prophylaxis. BALB/cfC3H mice represent animals which have become tolerant to tumor antigen via specific immunosuppression. Removal of the suppressive activity and induction of protective immunity with MAID in these mice to prevent tumor progression will be the model for treatment of animals with cancer predisposition. We propose to (1) test the effect of MAID-induced immunity on spontaneous mammary tumorigenesis, the progression of preneoplastic hyperplastic alveolar nodules (HAN) to tumor, and the development of metastasis from established tumors and (2) analyze and modulate the immune reactivity to MAID under two conditions of neoplastic development, namely in BALB/cfC3H mice which are chronically exposed to MMTV and develop mammary tumors spontaneously and in naive BALB/c mice which do not have prior exposure to MMTV.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Experimental Therapeutics Subcommittee 1 (ET)
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Barbara Ann Karmanos Cancer Institute
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Gill, R; Wang, H; Bluethmann, H et al. (1994) Activation of natural killer cells by mouse mammary tumor virus C4 in BALB/c and T-cell receptor V beta 2-transgenic mice. Cancer Res 54:1529-35
Wang, H; Gill, R F; Lichlyter, D et al. (1994) Deletion of CD4+ T cells and thymocytes by apoptosis in mouse mammary tumor virus (C4)-infected V beta 2 transgenic mice. Eur J Immunol 24:2950-6
Shakhov, A N; Wang, H; Acha-Orbea, H et al. (1993) A new infectious mammary tumor virus in the milk of mice implanted with C4 hyperplastic alveolar nodules. Eur J Immunol 23:2765-9
Wei, W Z; Gill, R F; Wang, H (1993) Mouse mammary tumor virus associated antigens and superantigens--immuno-molecular correlates of neoplastic progression. Semin Cancer Biol 4:205-13
Wei, W Z; Wang, H; Ficsor-Jacobs, R et al. (1992) Adoptive transfer of V beta 2-deleting activity with host cells from mice implanted with C4 preneoplastic hyperplastic alveolar nodules. Cancer Res 52:5183-9
Wei, W Z; Ficsor-Jacobs, R; Tsai, S J et al. (1991) Elimination of V beta 2 bearing T-cells in BALB/c mice implanted with syngeneic preneoplastic and neoplastic mammary lesions. Cancer Res 51:3331-3
Maloney, T; Wei, W Z (1990) Two-dimensional gel analysis of polypeptides from normal, preneoplastic and neoplastic mouse mammary tissues. Cancer Immunol Immunother 30:367-73
Wei, W Z; Fisher, S; Kohler, H (1989) Improved anti-tumor reactivity with monoclonal anti-idiotypic antibody conjugated to syngeneic mouse red blood cells. J Immunol Methods 122:227-34
Wei, W Z; Ratner, S (1987) A new assay to measure monoclonal antibody-dependent complement or macrophage-mediated tumor growth inhibition. J Immunol Methods 102:53-8