NORMAL HUMAN SERUM CONTAINS A NATURAL IGM ANTIBODY CYTOTOXIC FOR HUMAN NEUROBLASTOMA-CELLS

Neuroblastoma (NB) is characterized by the second highest spontaneous regression of any human malignant disorder, a phenomenon that remains to be elucidated. In this study, a survey of 94 normal human adult ser a revealed a considerable natural humoral cytotoxicity against human N B cell lines in approximately one-third of the tested sera of both gen ders. Specific cell killing by these sera,vas in the range of 40% to 9 5%. Serum cytotoxicity was dependent on an intact classical pathway of complement. By several lines of evidence, IgM antibodies were identif ied as the cytotoxic factor in the sera. Further analyses revealed tha t a 260-kDa protein was recognized by natural IgM of cytotoxic sera in Western blots of NB cell extracts. The antigen was expressed on the s urface of seven human NB cell lines but not on human melanoma or other control tumor cell lines derived from kidney, pancreas, colon, bone, skeletal muscle, lymphatic system, and bone marrow. Furthermore, no re activity was observed with normal human fibroblasts, melanocytes, and epidermal keratinocytes. The antigen was expressed in vivo as detected by immunohistochemistry in both the tumor of a NB patient and NB tumo rs established in nude rats from human NB cell lines. Most interesting ly, the IgM anti-NB antibody was absent from the sera of 11 human NB p atients with active disease. The anti-NB IgM also could not be detecte d in tumor tissue obtained from a NB patient. Collectively, our data s uggest the existence of a natural humoral immunological tumor defense mechanism, which could account for the in vivo phenomenon of spontaneo us NB tumor regression.