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 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.
Noguchi
M
M
First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Imaizumi
K
K
Kawabe
T
T
Wakayama
H
H
Horio
Y
Y
Sekido
Y
Y
Hara
T
T
Hashimoto
N
N
Takahashi
M
M
Shimokata
K
K
Hasegawa
Y
Y
D000818:Animals; D023201:CD40 Ligand / Q000235:genetics*; D019496:Cancer Vaccines; D018076:DNA, Complementary / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D018076:DNA, Complementary; D011994:Recombinant Proteins; D023201:CD40 Ligand; D007371:Interferon-gamma