Protein a treatment of cancer: Activation of a serum component with trans‐species anti‐B16 melanoma activity

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Abstract
Mice (C57BL) succumbed to cultured B16 melanoma cells i.p. with reproducible kinetics and an MST2 of about 26 days. Serum from tumour‐bearing or normal mice was treated at 0°C with fixed SAC cells and injected i.p. into fresh tumour‐bearing mice. If serum was given 7 days or less after B16 inoculation, the MST of the mice was highly significantly increased by up to 32%. Similar activity has been generated in normal human, rabbit and guinea‐pig serum, while untreated sera were ineffective. Apparently the sera contained an inactive native precursor that was activated by the SAC to produce an anti‐tumour agent. Precursor and product were both relatively labile at 0°C. Anti‐tumour activity was eluted at pH 2.5 from SAC or Sepharose‐protein‐A pretreated with serum, thus implicating the protein A component of SAC. The eluates contained haemolytically active Cl, the first component of complement, and five crude Cl preparations made by standard methods showed good anti‐tumour activity. However, seven other highly haemolytic Cl preparations had no anti‐tumour effect. Similarly, two crude preparations of the subcomponent Clq had good anti‐tumour activity, but eight other, more pure and highly haemolytic Clq preparations were inactive in mice. Thus the antitumour principle was not Cl or Clq alone, although it had some chemical properties in common with these substances. It remains unidentified, but has potential interest for cancer therapy.