β Scribed by Fred-Thomas Brezicka; Jan Holmgren; Inge Kalies; Leif Lindholm
No coin nor oath required. For personal study only.
Monoclonal antibodies (MAbs) reactive with the ganglioside fucosyl GM I (Fuc-GM I), an antigen associated with small-cell carcinoma of the lung (SCLC), were tested for their ability to mediate tumor-cell killing in vitro in conjunction with humoral and cellular effectors and to inhibit tumor engraftment in nude mice in vivo. MAbs F I 2 and F15, both IgG,,, induced human complement-mediated cytolysis of 3 Fuc-GM I -expressing tumor cell lines: one rat hepatoma cell line, H4-ll-E, and 2 human SCLC cell lines, NCI H69 and NCI H128. FI2 and F15 also induced ADCC of these cell lines in the presence of either murine or human effector cells. Addition of sub-cytolytic amounts of fresh human serum as complement source resulted in enhanced ADCC induced by MAb F I 2 (IgG,). Also a Fuc-GM Ireactive MAb of IgM isotype, F9, was able to induce such complement-aided ADCC (CADCC). F I 2 and F I5 both proved to effectively inhibit engraftment of H4-ll-E tumors in nude mice. A single dose of a modest amount (40 kg) of MAb conferred 65 to 100% protection against development of tumors. Our results demonstrate that Fuc-GMI can act as a target antigen on tumor cells for specific immunotherapy in vitro and in a mouse model in vivo. Complement and rnurine and human mononuclear effector cells were effective mediators of tumor cytolysis in vitro in the presence of murine Fuc-GM Ireactive MAbs. Our results also suggest that humoral and cellular effectors may co-operate in specific tumoricidal reactions and that these may be induced by antibodies of both IgG and IgM isotypes.
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