Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-gamma gene into lung cancer

CD40-CD40 ligand (CD40L) interaction is an Important costimulatory signalin g pathway in the crosstalk between T cells and antigen-presenting cells. Th is receptor-ligand system is known to be essential in eliciting strong cell ular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) tr ansduced with the CD40L gene (3LLSA-CD40L) were rejected in syngeneic C57BL /6 mice, but grew in CD40-deficient mice to the same extent as control tumo r cells. Immunohistochemical study showed that inflammatory cells, includin g CD4+, CD8+ T cells and NK cells, infiltrated Into the inoculated 3LLSA-CD 40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in th e induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C 57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 w eeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-gamma -transduced cells (3LLSA-IFN gamma) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results i ndicate that the in vivo priming with CD40L- and IFN-gamma gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity i n the treatment of lung cancer.