Protein A treatment of cancer: activation of a serum component with trans-species anti-B16 melanoma activity.
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 degree 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 degree 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 C1, the first component of complement, and five crude C1 preparations made by standard methods showed good anti-tumour activity. However, seven other highly haemolytic C1 preparations had no anti-tumour effect. Similarly, two crude preparations of the subcomponent C1q had good anti-tumour activity, but eight other, more pure and highly haemolytic C1q preparations were inactive in mice. Thus the anti-tumour principle was not C1 or C1q alone, although it had some chemical properties in common with these substances. It remains unidentified, but has potential interest for cancer therapy.
D000818:Animals; D002478:Cells, Cultured; D003166:Complement Activating Enzymes / Q000276:immunology; D003172:Complement C1 / Q000276:immunology; D015922:Complement C1q; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007113:Immunity, Innate; D007116:Immunization, Passive; D008297:Male; D008545:Melanoma / Q000097:blood / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000097:blood / Q000401:mortality / Q000628:therapy*; D011817:Rabbits; D013045:Species Specificity; D013205:Staphylococcal Protein A / Q000032:analysis / Q000276:immunology* / Q000627:therapeutic use
D003172:Complement C1; D007106:Immune Sera; D013205:Staphylococcal Protein A; D015922:Complement C1q; D003166:Complement Activating Enzymes