Local expression of secondary lymphoid tissue chemokine delivered by adeno-associated virus within the tumor bed stimulates strong anti-liver tumor immunity.
Development of an effective antitumor immune response depends on the appropriate interaction of effector and target cells. Thus, the expression of chemokines within the tumor may induce a more potent antitumor immune response. Secondary lymphoid tissue chemokine (SLC) is known to play a critical role in establishing a functional microenvironment in secondary lymphoid tissues. Its capacity to attract dendritic cells (DCs) and colocalize them with T cells makes it a good therapeutic candidate against cancer. In this study, we used SLC as a treatment for tumors established from a murine hepatocellular carcinoma model. SLC was encoded by recombinant adeno-associated virus (rAAV), a system chosen for the low host immunity and high efficiency of transduction, enabling long-term expression of the gene of interest. As a result, rAAV-SLC induced a significant delay of tumor progression, which was paralleled by a profound infiltration of DCs and activated CD4(+) T cells and CD8(+) T cells (CD3(+) CD69(+) cells) into the tumor site. In addition, rAAV-SLC treatment was also found to reduce tumor growth in nude mice, most likely due to inhibition of neoangiogenesis. In conclusion, local expression of SLC by rAAV represents a promising approach to induce immune-mediated regression of malignant tumors.
Liang
Chun-min
CM
Department of Anatomy and Histology and Embryology, Shanghai Medical College, Fudan University, 200032 Shanghai, People's Republic of China.
Zhong
Cui-ping
CP
Sun
Rui-xia
RX
Liu
Bin-bin
BB
Huang
Cheng
C
Qin
Jie
J
Zhou
Shuang
S
Shan
Junling
J
Liu
Yin-kun
YK
Ye
Sheng-long
SL
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014161:Transduction, Genetic; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D054421:Chemokine CCL21; D019742:Chemokines, CC; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C515479:Ccl21c protein, mouse