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Combined Effects of Chemotherapy and Immunity against Leukemia L1210 in DBA/2 Mice¹

Department of Experimental Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203

DBA/2 mice inoculated with the strain-specific leukemia L1210 survived more than 50 days as a result of the combined effects of drug treatments and immunity. Differences in L1210 immunogenicity were noted among 3 sublines of DBA/2 mouse strain. The therapeutic effects occurred also in DBA/2 sublines in which L1210 is weakly immunogenic and at drug doses which are immunodepressant per se.

More than 60% of DBA/2 Ha-DD mice inoculated with leukemia L1210 survived longer than 50 days after combined treatments with 4,4'-diacetyl-diphenyl-urea-bis(guanylhydrazone)dimethanesulfonate and arabinosylcytosine. The cured mice were resistant to reimplantation of L1210. This resistance was transferred to mice previously not exposed to the leukemia by the inoculation of immune serum, spleen or lymph node cells. The thereapeutic effects against L1210 were reduced in preirradiated hosts. DBA/2 Ha-DD mice were sensitized against L1210 also by repeated immunization with X-ray-killed leukemic cells. The incidence of chemotherapeutically induced cures was about 20 and 5% in DBA/2J and DBA/2Cr mice respectively. Also, in these sublines the cured mice were immune to L1210. Synergism between drugs and either passive or adoptive immunity were seen in both DBA/2Cr and DBA/2Ha-DD mice inoculated with serum or spleen cells from hyperimmune DBA/2Ha-DD mice.

Accelerated rejection of DBA/2J skin occurred in DBA/2Ha-DD mice immune to L1210. DBA/2Ha-DD mice could be sensitized against L1210 by immunization with DBA/2J or DBA/2Cr skin grafts. The survival of reciprocal skin grafts between DBA/2J and DBA/2Ha-DD mice was prolonged by the 2 drugs at doses exerting therapeutic effects against L1210. The antileukemic effects of the 2 drugs were reduced by pretreatments with the same drugs at therapeutic doses.

¹ This investigation was supported in part by a research grant (CA 04130) from the National Cancer Institute, USPHS.

Received 8/16/68. Accepted 12/ 5/68.

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