Interleukin-2 activation of human bone marrow in long-term cultures: an effective strategy for purging and generation of anti-tumor cytotoxic effectors.
Our previous studies have shown that IL-2 activated bone marrow cells develop potent tumoricidal activity in vitro and in vivo. With the dual aim of in vitro purging and generation of effectors which could mediate graft-versus-leukemia effects in vivo, IL-2 activation of human bone marrow in long-term cultures (LTC) was tested. Marked cytotoxicity was seen against A375 (melanoma), K562 (CML) and Daudi (lymphoma) cell lines in IL-2 (1000 U/ml) stimulated cultures. Hematopoietic progenitor cell number in these cultures was assessed by day 14 clonogenic assays. In 1-week-old IL-2 stimulated cultures a higher number of clonogenic cells was seen than control LTCs without IL-2. However, thereafter accelerated decrease in the number of clonogenic cells was seen in IL-2 cultures. In vitro purging efficacy was tested by elimination of A375 and K562 cells mixed with normal marrow at 1:10 and 1:100 ratios and co-cultured for 10 days. In IL-2 stimulated cultures, A375 cells capable of proliferation were not detectable at both mixing ratios. K562 elimination was complete only at 1:100 ratio. After 10 days in culture, no Ph1-positive metaphases were seen in IL-2 stimulated BM cultures of 4 patients with CML. These results indicate that IL-2 activation of BM in 1-2 week cultures can lead to generation of marked anti-tumor cytotoxicity and effective in vitro purging in a variety of tumor types.
Verma
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Bone Marrow Transplantation Program, Lombardi Cancer Research Center, Georgetown University, Washington, DC 20007.
Bagg
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A
Brown
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Mazumder
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D001853:Bone Marrow / Q000473:pathology* / Q000502:physiology; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002455:Cell Division; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy; D008223:Lymphoma / Q000473:pathology / Q000628:therapy; D008545:Melanoma / Q000473:pathology / Q000628:therapy; D010641:Phenotype; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007376:Interleukin-2