Natural Polyclonality of Spontaneous AKR Leukemia and Its Consequences for So-Called Specific Immunotherapy2

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Abstract
Young female AKR mice made leukemic by iv inoculation of 103 spontaneous AKR thymoma cells were treated with repeated injections of irradiated cells from the same tumor. Treatment began 1 day after injection of the viable cells. The cytotoxicity of sera and lymphoid cells from healthy mice immunized with lymphoma cells from either treated or non treated mice with leukemia grafts revealed that the tumor cells could be subdivided into four distinct antigenic types. One type (clone A) accounted for about 97% of the lymphoma cells in each mouse with spontaneous leukemia, whereas the remaining 3% were subdivided into three other distinct antigenic types (clones B, C, and D). Lymphoma cells from treated mice with grafted leukemia were never clone A type but either clone B, C, or D type. Repeated sc injections of 107 irradiated cells from spontaneous AKR thymomas induced from 15 to 34% cure in mice with grafts of leukemia cells. Treatment with only clone A induced about 32% cure, whereas treatment with clone B, C, or D had no beneficial effect. Treatment with 107 cells each of clone A plus clone B gave 33% cure; clone A pius clone B plus clone C, 45%; and all four clones cured 92% of the mice with leukemia grafts. The efficiency of immunotherapy may be influenced by the natural clonality of the tumor to be treated.

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