Intratumoral Therapy with Cytokine Gene-Modified Dendritic Cells in Murine Lung Cancer Models

The central importance of functional host professional antigen-presenting cell (APC) in the immune response against cancer has been well-defined (1 ). Dendritic cells (DC) are highly specialized professional APC with potent capacity to capture, process, and present antigen to T cells (2 ). Unfortunately, tumor cells interfere with host DC maturation and function (3 ). To circumvent tumor-mediated inhibition of DC maturation and function in vivo, DC that have undergone cytokine-stimulated maturation ex vivo have been effectively utilized in clinical trials and murine cancer models (4 –8 ) Antigen-specific cytotoxic T lymphocytes (CTL) responses have been achieved utilizing ex vivo antigen-pulsed DC (5 ,9 –11 ). Additionally, novel tumor antigen-delivery systems utilizing cytokine gene-transduced tumor cells and DC (4 ,7 ) or fusion of tumor cells with DC have resulted in induction of antitumor immunity (12 ,13 ). Delivery of tumor antigens by ex vivo stimulated DC has been shown to be superior to purified peptides in avoiding CTL tolerization (14 ). Vaccination with multiple tumor antigens may be superior to the use of a single epitope (15 ,16 ) and these responses can be further enhanced by the co-administration of immune-potentiating cytokines (4 ,7 ). We have demonstrated previously that interleukin (IL)-7-transduced tumor cells administered intratumorally in conjunction with DC elicit potent antitumor responses in a murine model of established lung cancer (7 ).