Immunotherapeutic effects of purified mistletoe lectin (ML-I) on murine large cell lymphoma

Abstract

The immune system in the tumor bearing host, particularly those with advanced disease, is deficient in eliciting specific or non-specific immune response against an immunogen including its own tumor associated antigens. This decreased immune response is thought to play an important role in tumor progression-metastasis which results in the death of tumor bearing host (Lovett et al., 1982; Joshi et al., 1991; Messbarger and Joshi, 1991). Therefore, an effective in vivo immunomodulator/ immunostimulator would increase the host’s immune defense mechanism which, in turn, would help in decreasing tumor growth and their metastasis. Among the different types of modulators, specific binding of carbohydrate moieties to cellular glycoconjugates such as endogenous lectin is increasingly gaining attention (Leiner et al., 1986; Olden and Parent, 1987; Gabius, 1988a; 1988b). Some plant lectins/products have beneficial effects on modulating the immune system (Hajto et al., 1986). The proprietary mistletoe extract, Iscador, has an immunomodulatory action in humans and in rabbits (Nienhaus and Leroi, 1970; Nienhaus et al., 1970; Rentea et al., 1981; Kwaja et al., 1981; Blokshma et al., 1982; Hajto et al., 1986; 1989; 1990; Gabius et al., 1990a; 1990b). Except for the last two reports by Hajto et al. (1989; 1990), the rest of the studies on mistletoe were based on crude mistletoe extract. The purified mistletoe lectin ML-I, is a β-galactoside specific lectin with an approximate molecular mass of 63 kD. ML-I consist of two subunits with different functional domains, the toxic subunit with an apparent molecular weight of 29 kD, termed A, and the carbohydrate-binding (β-galactoside specific) subunit with an apparent molecular weight of 34 kD, termed B.