Hidden complement-dependent cytotoxins were demonstrated in normal donor sera after removing anti-immunoglobulins that normally block the ability of these immunoglobulin Gs to react with surface antigens on tumor cells. The blocking antibodies had certain properties of anti-idiotypes. Immunoglobulin G from Cohn Fraction II, after removing these antiimmunoglobulins, was cytotoxic for cultured fetal cells and for malignant melanoma, breast, lung, colon, and other tumor cells maintained either in tissue culture or by serial passage in nude mice. The cytotoxins were not adsorbed by extracts from normal lymphoid, liver, skin, or red blood cells. These results suggest that a heterogeneous group of natural antibodies reactive with antigens expressed on a variety of neoplastic and fetal cells circulate in normal donor sera as part of a soluble immune complex, together with a blocking anti-immunoglobulin.

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Supported by NIH Grants CA20543, CA05831, and CA15333, Kelsey Seybold Foundation, and Stehlin Foundation for Cancer Research.

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