Several studies in mice have demonstrated a correlation between antibody induction and tumor growth inhibition in vaccinated mice. Early studies have shown a correlation between antibody formation to Moloney sarcoma virus and regression of virus-induced sarcomas (45). Tumor growth inhibition was mediated by ADCC. Similarly, cytotoxic antibodies to feline sarcoma virus have been implicated in tumor regression of virus-induced sarcomas in dogs (46).
Anti-idiotypic antibodies binding to the antigen-combining site of antitumor antibodies may mimic tumor antigen and induce antitumor immunity (reviewed in ref. 47). By virtue of tumor antigen mimicry, anti-idiotypic antibodies may break immunological tolerance to tumor-associated antigens that are also expressed by normal tissues (47). Wikstrand et al. (48) have recently shown that anti-idiotypic antibodies mimicking mutated epidermal growth factor receptor (EGF-RvIII) can induce EGF-RvIII-specific antibodies in mice, which protect the animals from the growth of established tumors. A recombinant vaccinia virus containing the human papillomavirus E2 protein has been shown to promote tumor regression by stimulating antibody-dependent macrophage-mediated cytotoxicity (49). Augmentation of immunoglobulin (Ig)M titers to sLe(x) and GM3 after immunization with bacille Calmette-Guerin (BCG), or with tumor cells with BCG correlated with retarded tumor growth in mice, whereas increased IgG titers to sLe(x) significantly correlated with aggressive tumor growth in mice immunized with cells without adjuvants (50). The mechanism of how antibodies can accelerate tumor growth is poorly understood.
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