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Immunotherapy of Cancer with L-Phenylalanine Mustard as a Hapten¹

Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

An antiserum produced in Wistar rats with an L-phenylalanine mustard (PhM)-conjugated extract of Walker 256 carcinosarcoma, which had been confirmed to be specific against tumor extract, PhM alone, and PhM-tumor conjugate, was used in this study. Seven groups of Wistar rats with established Walker tumor (mean volume, 5.2 cu cm) were treated as follows: (a) by intratumoral (i.t.) injection of PhM plus i.v. injection of antiserum; (b) by injection of PhM (i.t.) plus 0.9% NaCl solution (i.v.); (c) by injection of 0.9% NaCl solution (i.t.) plus antiserum (i.v.); (d) by injection of PhM (i.t.) plus 0.9% NaCl solution (i.v.) plus hydrocortisone (i.m. for 10 days); (e) by injection of PhM (i.t.) plus antiserum (i.v.) plus hydrocortisone (i.m. for 10 days); (f) by injection of PhM (i.m.); or (g) no treatment. All surviving rats were sacrificed 90 days after tumor transplantation. PhM-antiserum treatment induced complete regression of tumor in 7 of 8 rats, with a significant increase in mean survival time. PhM (i.t.) treatment induced regression in some animals, but at a much slower rate, and the mean survival time of this group was significantly shorter than that of the PhM-antiserum group. Antiserum (i.v.) treatment and PhM (i.m.) treatment showed no regressive effect. The addition of an immunosuppressant, hydrocortisone, eliminated the tumor-regressive effect of both PhM and PhM-antiserum treatment. Similar results were obtained in rats with significantly larger tumors. These results indicate that PhM-antiserum immunotherapy can produce complete tumor regression.

¹ This work was supported in part by Grant RR-00322 from the General Clinical Research Centers Program of the Division of Research Resources, NIH, and by American Cancer Society Institutional Grant IN-38-L.

Received 10/24/72. Accepted 5/ 4/73.