Immunotherapeutic approaches to leukemia: the use of the Friend virus-induced erythroleukemia model system.
We have developed a model system to study immunologically mediated regression of leukemia based on Friend virus-induced erythroleukemias. This system has been used to evaluate the immunotherapeutic activity of macrophages, specifically reactive T-cells (CTL/RFB), lymphokine-activated killer cells and interleukin 2, and tumor necrosis factor alpha and interferon-gamma. In the present studies, CTL/RFB were evaluated for their ability to prevent disease recurrence. Animals with the regressing strain of Friend virus at Day 39 post virus were treated with either one or two injections of 5 x 10(6) CTL/RFB. Animals given one or two injections of CTL/RFB had a significantly lower rate of recurrence than did untreated animals. The helper T-cell component of CTL/RFB was implicated in causing leukemia regression. Interleukin 1 alpha and tumor necrosis factor alpha, multifunctional cytokines with similar biological activities, were evaluated for their ability to suppress leukemic erythroid colony-forming cells and induce regression. Interleukin 1 alpha suppressed the conventional strain of, but not the polycythemia-inducing strain of, Friend virus-leukemic late erythroid colony-forming units and caused only a temporary regression of disease, while tumor necrosis factor alpha suppressed both forms of the disease and with multiple inoculations could cause permanent disease regressions. This system provides an excellent model for examining the efficacy of immunotherapy of leukemias with various mediators and effector mechanisms.
Johnson
C S
CS
Department of Otolaryngology, University of Pittsburgh, School of Medicine, Pennsylvania 15213.
Chang
M J
MJ
Thurlow
S M
SM
Pourbohloul
S C
SC
Furmanski
P
P
D000818:Animals; D005622:Friend murine leukemia virus; D006410:Hematopoiesis / Q000187:drug effects; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use; D007375:Interleukin-1 / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma