The efficacy of bone marrow transplantation (BMT) for the prevention of 90Y toxicity and extension of survival in nude mice with i.p. LS174T carcinomatosis was evaluated. 90Y-labeled monoclonal antibody (MAB) directed against carcinoembryonic antigen (90Y-anti-CEA MAB) at a dose of 120 μCi caused no deaths due to treatment toxicity and increased the duration of animal survival. No long term cures were obtained in these mice. At doses of 160 μCi or more 90Y-anti-CEA MAB led to hematological deaths.

Nude mice were given i.p. injections of 106 LS174T tumor cells on day 0. On day 7 the mice received 90Y-anti-CEA MAB i.p. at doses of 120–225 μCi. Syngeneic bone marrow cells (107 cells) were then injected i.v. into the mice at 1, 3, 5, 7, 10, or 14 days following 90Y treatment. In the absence of BMT, toxic deaths for animals given 175 μCi 90Y were 11 of 24 (46%) with a median survival of 17 days and 13 of 20 (65%) for animals given 225 μCi 90Y with a median survival of 14 days. Animals receiving the same two doses of 90Y and given BMT 5 days following the 90Y treatment showed 0 of 24 (0%) and 0 of 54 (0%) toxicity deaths, respectively. The optimal time of BMT in relation to 90Y therapy was dependent upon the dose of 90Y-anti-CEA MAB (225 μCi, 3–5 days; 175 μCi, 5–14 days). The mean survival in tumor bearing animals was extended from 31.7 ± 1.2 (SE) to 45.3 ± 2.0 days by treatment with 120 μCi of 90Y-anti-CEA MAB. By increasing the dose of 90Y-anti-CEA MAB to 225 μCi and undertaking BMT 5 days later the mean survival was further extended to 63.2 ± 3.6 days (P < 0.005). BMT administered at the optimal times can prevent toxic deaths and facilitates higher, more effective doses of tumor specific 90Y-MAB.

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Presented at the “Second Conference on Radioimmunodetection and Radioimmunotherapy of Cancer,” September 8–10, 1988, Princeton, NJ. This study was supported in part by a grant from the Margaret Early Foundation, Los Angeles, CA; NIH Training Grant CA09477; Cancer Center Core Grant CA 33572; Program Project Grant CA 43904; and a grant from Hybritech, Inc., San Diego, CA.

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