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Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-Ikebukuro, 1-37-1, Toshima-ku, Tokyo 170, Japan
Inoculations (twice) of L1210 murine leukemic vaccine prepared in the presence of glutaraldehyde and concanavalin A induced resistance in BALB/c x DBA/2 F1 mice against a subsequent challenge by 103 live L1210 cells. Administration of cyclophosphamide (CY) before the second vaccination enhanced the production of resistance in mice by L1210 vaccine. This enhancement was dependent on the dose of CY, the timing of CY administration, and the vaccine preparations. CY (100 mg/kg) administered on either day of Day -1 to Day -3 of the second vaccination, although not of the first vaccination, produced enhancement. Vaccine-bound concanavalin A was essential for the production of synergistically enhanced immunity by the vaccine and CY. Kinetic study showed that enhancement was derived from the net increase of immune response, not from the earlier production of the maximal response inducible by the vaccine. Enhanced immune resistance by L1210 vaccine and CY was specific for L1210 leukemia, as evidenced by a lack of resistance to a subsequent challenge with P388 leukemic cells. Peritoneal exudate cells, not spleen cells, seem responsible for enhanced immunity. With agent specificity, other chemotherapeutic agents including mitomycin C, Adriamycin, methotrexate, and 5-fluorouracil induced enhancement of L1210 vaccine-induced immune resistance, whereas 1-ß-D-arabinofuranosylcytosine, 6-mercaptopurine, and 6-thioguanine did not.
1 This research was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare and Ministry of Education, Science, and Culture, Japan.
Received 11/ 4/77. Accepted 1/31/78.
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