Experimental therapy of human breast tumors with 131I-labeled monoclonal antibodies prepared against the human milk fat globule.
Breast tumors are susceptible to attack by unconjugated anti-human milk fat globule monoclonal antibodies (MoAbs) and most particularly by their mixture (cocktail) (Cancer Res., 47: 532-540, 1987). In the present study the same MoAbs (Mc1, Mc3, Mc5, and Mc8) labeled with 131I, either singly or in cocktails, were used for a similar purpose. Biodistribution studies showed that a transplantable human breast tumor line (MX-1) implanted in BALB/c nude mice (nu/nu) had the maximum incorporation of injected 131I-MoAbs at day 4 while levels in circulation and in normal tissue declined steadily from day 1. Also, these studies showed that the amount of radiolabeled Mc3 MoAb incorporated by MX-1 tumors was greater than that for cocktail of MoAbs and MoAb Mc5. Tumor destruction by injected 131I-MoAb cocktail was shown in therapy experiments to be dose dependent. A single injection (1500 [corrected] microCi/mouse) of 131I-MoAb Mc3, or of cocktail, produced large breast tumor volume diminution and inhibition of growth for up to 30 days while a similar dose of 131I-labeled control IgG had no effect. A second dose of 1500 [corrected] microCi 131I-MoAb of Mc3 or of cocktail, injected at an appropriate interval, again diminished tumor mass significantly and inhibited its growth for another 20 days. In control experiments, non-breast tumors (colon) were marginally affected by the 131I-MoAbs. These results show that the systemic injection of radioiodinated MoAbs against human milk fat globule destroy the epithelial cells of human breast tumors and control their growth for an appreciable length of time. Radioiodoconjugated MoAbs proved to be more effective than unconjugated MoAbs in reducing breast tumor mass and also in inhibiting growth for longer periods of time at immunoglobulin doses 100 to 200 times lower. Further exploration of their role in breast cancer treatment seems warranted by these results.
Ceriani
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John Muir Cancer and Aging Research Institute, Walnut Creek, California 94596.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D018396:Mucin-1