BALB/C mice injected with LSTRA leukemic cell line are cured by in vivo treatment with IL-2 + GM-CSF.
We studied the effects of the in vivo administration of interleukin-2 (IL-2) (at low doses) + GM-CSF in BALB/C mice injected intraperitoneally with LSTRA murine leukemic cell line in order to test the possible role of this immunotherapeutic approach in the eradication of leukemia. Mice were injected intraperitoneally on day -1 with different concentrations of LSTRA cells. On day 0, mice received a lethal dose of TBI of 700 cGy from a Cs(137) source, followed by a single high dose of recombinant human-granulocyte-colony stimulating factor (rh-G-CSF) (1 microg/g) intraperitoneally 2h after TBI. This procedure rescued 80% of mice but only mice injected with the lower concentration of LSTRA cells (10(3)) could be cured. The lethal dose (LD 100/60) of LSTRA in normal mice was 10(4). The subcutaneous administration of rh-IL-2 (4.000 IU/mouse per day, from day +1 to +28) + rm-GM-CSF (1 microg/kg per day) from day +7 to +28 cured mice injected with 10(4) LSTRA cells and 40% of mice injected with 10(5) cells. Mice injected with 10(6) cells died from leukemia. We observed an increase in LAK activity on days +21 and +28 without an increase in NK activity. We show that BALB/C mice injected with LSTRA cell line can be cured by in vivo activation with IL-2 + GM-CSF depending on the cell dose injected. The curability of leukemia was confirmed at the molecular level with a PCR method.
Rojas
R
R
Department of Hematology, Reina Sofi;a University Hospital, Avda Menéndez Pidal s/n, 14004 Córdoba, Spain. md1togoa@uco.es
Roman
J
J
Herrera
C
C
Alvarez
M A
MA
Ramirez
R
R
Torres
A
A
D000818:Animals; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual / Q000175:diagnosis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor