RRC ID 4774
Author Noguchi M, Imaizumi K, Kawabe T, Wakayama H, Horio Y, Sekido Y, Hara T, Hashimoto N, Takahashi M, Shimokata K, Hasegawa Y.
Title Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-gamma gene into lung cancer.
Journal Cancer Gene Ther.
Abstract CD40-CD40 ligand (CD40L) interaction is an important costimulatory signaling pathway in the crosstalk between T cells and antigen-presenting cells. This receptor-ligand system is known to be essential in eliciting strong cellular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) transduced 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 tumor cells. Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in the induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 weeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-gamma-transduced cells (3LLSA-IFNgamma) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results indicate that the in vivo priming with CD40L- and IFN-gamma gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer.
Volume 8(6)
Pages 421-9
Published 2001-6
DOI 10.1038/sj.cgt.7700320
PMID 11498762
MeSH Animals CD40 Ligand / genetics* Cancer Vaccines* DNA, Complementary / metabolism Genetic Therapy / methods* Immunohistochemistry Interferon-gamma / genetics* Interferon-gamma / metabolism Lung Neoplasms / genetics* Lung Neoplasms / therapy* Mice Mice, Inbred C57BL Recombinant Proteins / metabolism Spleen / metabolism T-Lymphocytes, Cytotoxic / metabolism Time Factors Transduction, Genetic* Transfection Tumor Cells, Cultured
IF 4.044
Times Cited 20
DNA material pBluescript KS+mIFN gamma (RDB01482)