Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factorand interferon-gamma

Adoptive transfer of activated macrophages, being both effector cells and a ntigen-presenting cells, represents a promising approach to immunotherapy o f cancer. In order to get activated macrophages with increased antitumor po tential, in the present study, murine peritoneal macrophages were transduce d with human macrophage colony-stimulating factor (IM-CSF) and murine inter feron-gamma (IFN gamma) by recombinant adenovirus infection. The results de monstrate that M-CSF and IFN gamma gene-modified macrophages exhibited high er expression of MHC-II, B7.1 and ICAM-1, increased antigen-presenting acti vity and cytotoxicity. It was also shown that they secreted more tumor necr osis factor, interleukin-1 and nitric oxide. In vivo experiments showed tha t in previously initiated murine pulmonary metastatic melanoma, tumor lysat e-pulsed, M-CSF and IFN gamma gene-modified macrophages elicited more poten t antitumor effects than tumor lysate pulsed M-CSF or IFN gamma gene-modifi ed macrophages. Cytotoxic T lymphocyte (CTL) activity, IFN gamma and tumor- necrosis factor production of the splenocytes increased significantly in mi ce after intravenous injection of the gene-modified macrophages. M-CSF and IFN gamma gene-modified macrophages may act as activated effector and antig en-presenting cells, thus eliciting a more potent antitumor response.