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A Study of the Preparation, Localization, and Effects of Antitumor Antibodies Labeled with I^131*

( Departments of Pathology and Medicine and the Argonne Cancer Research Hospital, University of Chicago, Chicago, Ill.)

Multiple injections of lyophilized rat tumor tissue given to rabbits by multiple portals and preceded by a single intramuscular injection of the same material in Freund's adjuvant resulted in unusually potent and fairly specific antitumor antisera. The characteristics of these antisera have been investigated in vitro by means of complement fixation or by labeling the specific -globulin with I¹³¹ and determining the amount that combines with insoluble components of the tumor. The specific antitumor antibodies became more apparent following purification of the labeled -globulin by means of elution with additional unlabeled antitumor sera. There was an almost complete in vitro cross-reaction between antiserum produced to Flexner-Jobling tumor and Jensen sarcoma.

Intravenous injection of the eluted I¹³¹ antitumor -globulin into rats bearing the homologous tumor resulted in slight selective localization of the I¹³¹ -globulin in the tumor as compared with the localization of similarly labeled normal -globulin. However, there was always much greater localization of the antitumor -globulin in the liver and other organs. This failure of selective localization is probably due to the low permeability of the blood vessels of the tumor to the large antibody globulin molecules. When labeled antibodies to Ehrlich ascites tumor were injected intraperitoneally into mice bearing proliferating ascites tumors, the labeled antibody globulin was clearly differentially localized on the tumor cells.

Although the growth of the Ehrlich ascites tumor can apparently be retarded by the specific eluted I¹³¹-labeled -globulin, no increase in survival time has been demonstrated, probably because of the toxicity of the labeled antibody.

The toxicity of the intraperitoneally injected labeled antiserum preparation for the tumor-bearing mouse varies inversely with amount of tumor-growing in the mouse.

Fasting of the mice during the period following injection of the labeled antiserum increases the localization of the specific antibodies on the tumor cells.

A synergism between the effects of the attached radioactivity and the toxic action of the antibody has not yet been demonstrated. With a more radiosensitive tumor and with better in vitro methods of increasing the specificity of the antiserum, a study of this combined carcinocidal approach should be possible.

^* Supported in part by an institutional grant from the American Cancer Society.

Received 2/10/56.