title: Adoptive therapy of established syngeneic leukemia by cells primarily sensitized in vitro.
abstract: The aim of the current studies was to determine whether cells primarily sensitized in vitro are effective in adoptive therapy of established tumors. Spleen cells from normal BALB/c mice were cultured for 5 days at variable responder:stimulator ratios with an X-irradiated syngeneic Moloney virus-induced leukemia (LSTRA), denoted as BALB/c.(LSTRA)x, or with X-irradiated normal BALB/c spleen cells, denoted as BALB/c. (BALB/C)x, and tested for ability to eradicate an established lethal inoculum of LSTRA in adaptive chemoimmunotherapy. BALB/c mice inoculated with 2 X 10(3) LSTRA i.p. on Day 0 were treated on Day 5 with cyclophosphamide (180 mg/kg) plus 1 X 10(7) cultured cells. Treatment with cyclophosphamide alone cured only 3% of mice. As an adjunct to cyclophosphamide, therapy with BALB/c.(BALB/c)x cultured at responder:stimulator ratios of 8:1, 32:1, and 128:1 cured 29%, 37%, and 33% of mice, respectively; and BALB/c.(LSTRA)x cultured at the same responder:stimulator ratios cured 54, 83, and 29% of mice, respectively. Furthermore, the therapeutic efficacy of BALB/c.(LSTRA)x was abrogated by treatment with anti-Thy 1.2 + complement. Thus, culture of normal lymphoid cells with tumor at optimal responder:stimulator ratios substantially enhanced their ability to eradicate established tumor, and the enhanced therapeutic efficacy was mediated by a T-cell generated during culture. The specificity of primary in vitro sensitization in generating cells effective in the therapy of established tumors was confirmed by treating BALB/CH-2d X C57BL/6H-2b F1 (hereafter called B6F1) mice bearing either LSTRAH-2d or an antigenically distinct chemically induced leukemia, EL-4(G-)H-2b, with CB6F1 spleen cells sensitized in vitro to either of the parental tumors.
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000627:therapeutic use; D003584:Cytological Techniques; D007116:Immunization, Passive; D007158:Immunologic Techniques; D007942:Leukemia, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D013154:Spleen / Q000528:radiation effects / Q000637:transplantation; D014185:Transplantation, Isogeneic
chemical_list: D003520:Cyclophosphamide