Adenovirus-mediated LIGHT gene modification in murine B-cell lymphoma elicits a potent antitumor effect.
Here, we investigated the antitumor effect of adenovirus-mediated gene transfer of LIGHT, the tumor-necrosis factor (TNF) superfamily member also known as TNFSF14, in the murine A20 B-cell lymphoma. LIGHT gene modification resulted in upregulated expression of Fas and the accessory molecule--intercellular adhesion molecule-1 (ICAM-1) on A20 cells and led to enhanced A20 cell apoptosis. LIGHT-modified A20 cells effectively stimulated the proliferation of T lymphocytes and interferon (IFN)-gamma production in vitro. Immunization of BALB/c mice with a LIGHT-modified A20 cell vaccine efficiently elicited protective immunity against challenge with the parental tumor cell line. Adenovirus-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against pre-existing A20 cell lymphoma in BALB/c mice. This adenovirus-mediated LIGHT therapy induced substantial splenic natural killer (NK) and cytotoxic T lymphocyte (CTL) activity, enhanced tumor infiltration by inflammatory cells and increased chemokine expression of CC chemokine ligand 21 (CCL21), IFN-inducible protein-10 (IP-10) and monokine induced by IFN-gamma (Mig) from tumor tissues. Thus, adenovirus-mediated LIGHT therapy might have potential utility for the prevention and treatment of B-cell lymphoma.
Hu
Guili
G
Institute of Immunology, Zhejiang University, Hangzhou, China.
Liu
Yang
Y
Li
Hong
H
Zhao
Dekuang
D
Yang
Liuqing
L
Shen
Jiangen
J
Hong
Xuejun
X
Cao
Xuetao
X
Wang
Qingqing
Q
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007114:Immunization; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics* / Q000627:therapeutic use*
D019496:Cancer Vaccines; D018925:Chemokines; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14