Advertisement
Free access | 10.1172/JCI110648
Department of Surgery and Pathology, University of Toronto, Ontario, Canada M5S 1A8
Find articles by Falk, R. in: JCI | PubMed | Google Scholar
Department of Surgery and Pathology, University of Toronto, Ontario, Canada M5S 1A8
Find articles by Hardy, M. in: JCI | PubMed | Google Scholar
Department of Surgery and Pathology, University of Toronto, Ontario, Canada M5S 1A8
Find articles by Makowka, L. in: JCI | PubMed | Google Scholar
Department of Surgery and Pathology, University of Toronto, Ontario, Canada M5S 1A8
Find articles by Teodorczyk-Injeyan, J. in: JCI | PubMed | Google Scholar
Department of Surgery and Pathology, University of Toronto, Ontario, Canada M5S 1A8
Find articles by Falk, J. in: JCI | PubMed | Google Scholar
Published September 1, 1982 - More info
This report describes a novel method of immunochemotherapy; the active immunization to the drug 5-fluorouracil (5-FU) with enhanced antitumor activity resulting from its subsequent systemic administration. Two metastasizing carcinomas in the Fischer strain (F344) rat have been used: a chemically induced bladder carcinoma (FBCa) and a spontaneous mammary adenocarcinoma (MACa). Both tumors grow rapidly and result in 100% mortality within 10 wk of implantation. Neither tumor is sensitive to systemic 5-FU alone. Intradermal sensitization to 5-FU before FBCa tumor implantation, followed by 5-FU administered systemically, resulted in significant tumor regression and improvement in survival with eradication of all tumor and cure in 20% of animals. A similar antitumor effect was observed with the MACa. A comparable drug effect was observed when methotrexate sensitization was given before FBCa implantation followed by systemic MTX. Specificity to the sensitizing drug was demonstrated by the lack of effect of sensitization with either 5-FU or MTX unless followed by systemic therapy with the requisite sensitizing agent. Sensitization to 5-FU has also been assessed after FBCa implantation followed by resection of the local tumor. Resection was performed after distant tumor metastases had occurred, and was followed by systemic 5-FU therapy. Whereas tumor resection alone failed to cure any animal, sensitization to 5-FU increased cure rate fourfold over animals receiving systemic 5-FU alone. Antibody to 5-FU in the sera of sensitized animals has been suggested by an immunoenzymatic staining technique and its specificity confirmed in a radioimmunoassay. It is postulated that a combination of the systemic agent and the antibody elicited to it by sensitization produces the significant antitumor effect observed. The antitumor effect observed with this new approach to immunochemotherapy warrants further experimental and clinical study.