The effect of prior injections of tissue antiserums on the survival of cancer homoiografts in mice.

1. Rabbits: Three rabbits received a total of six injections at 4-day intervals. The first injection was intraperi toneal. In subsequent injections the antigen homogenates were divided into two halves by light centrifugation. The sediment was in jected intraperitoneally in the morning, in amounts of 1.0, 1.5, 2.0, 2.0, and 2.0 ml. in order, in each of the five injections; 0.5 ml. of the supernate was injected intravenously 4-6 hours later. This procedure lessened the incidence of allergic manifestations in the rabbits. 2. Mice: Fifty C57 black/6Ks mice, about 3 months old, equally divided by sex and of equiv alent weight, received six intraperitoneal injec tions of 0.5 ml. each of the whole tissue homoge nates during a 2-week period. Antiserums.—The rabbits were bled by cardiac puncture, under intravenous nembutal anesthesia (30 mg/kg of body weight). The mice were bled by tail vein incision. The serums were separated, titrated for antibody presence by agglutination of erythrocytes from strain A mice, and lyophilized. Prior to injection into the experimental ani mals, the antiserums were reconstituted with sterile double-distilled water. Hemagglutinin titers for the rabbit antiserums were as follows: rabbit No. 1, 1:5120; rabbit No. 2, 1:128; rabbit No. 3, 1:512. The titer for the antiserum produced in the C57 black/6Ks mice was 1:256. Experimental procedure.—The host mice (C57 black/6Ks) received five intraperitoneal injections of 0.5 ml. each of the reconstituted antiserums over a 2f-week period. Live tumor was inoculated subcutaneously in the suprascapular region by trocar, under aseptic conditions, 7 days after the last injection of antiserum. The course of subse quent growth of the grafts was followed twice weekly by palpation for 1 month, and weekly It had been previously noted (2) that prior in jections of lyophilized normal and cancerous mouse tissues resulted either in break-down of host resistance, as evidenced by positive takes of tumor grafts, or in enhanced host resistance, evi denced by the failure of tumor takes. Whether enhancement or inhibition occurred was related to the dose of lyophilized tissue injected (1). In investigations dealing with wound healing, it was found that the process of healing could be accelerated or retarded by dose gradation of tissue antiserum injections, administered immediately after wounding (3, 4). The investigations reported here are directed to the question of whether the observed experi mental alterations in normal tissue growth (wound healing) and cancerous tissue growth (tumor homoiografts) are under the control of common host mechanisms. To this end, a study was made of the effects of prior injections of tissue antiserums on the growth of cancer homoiografts in mice.