Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice.
A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D018845:CD11 Antigens / Q000032:analysis; D018821:CD18 Antigens / Q000032:analysis; D002455:Cell Division; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D005819:Genetic Markers; D015316:Genetic Therapy; D005822:Genetic Vectors; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D019868:Kanamycin Kinase; D007942:Leukemia, Experimental / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D007951:Leukemia, Myeloid / Q000628:therapy*; D051379:Mice; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011961:Receptors, Fc / Q000032:analysis; D012190:Retroviridae; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D018845:CD11 Antigens; D018821:CD18 Antigens; D017931:DNA Primers; D005819:Genetic Markers; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase