An anti-double-stranded DNA monoclonal antibody induced by tumor cell-derived DNA inhibits the growth of tumor in vitro and in vivo via triggering apoptosis.
Serological presence of anti-double-stranded DNA (anti-dsDNA) antibodies is a common phenomenon in cancer patients. Some patients with relatively high levels of anti-dsDNA antibodies may have a better prognosis, indicating the potential antitumor roles of anti-dsDNA antibodies. To delineate the role and mechanisms of anti-dsDNA antibodies in delaying tumor development, here we prepared a panel of anti-dsDNA monoclonal antibodies (mAbs) and assessed their antitumor effects both in vitro and in vivo. After immunization of BALB/c mice with DNA from SP2/0 tumor cells, 12 anti-dsDNA mAbs were obtained. Among these mAbs, mAb 2G8 exhibited the strongest cytotoxicity to Wehi164 cells in vitro and significantly inhibited the growth of tumor in vivo. This mAb 2G8-mediated antitumor effect was mainly exerted by triggering apoptosis, as evidenced by Annexin V staining and DNA fragmentation. Further, the expression of antiapoptotic genes Bcl-2 and Bcl-xL was downregulated while that of pro-apoptotic gene Bax was upregulated, suggesting the involvement of mitochondrial apoptotic pathway. Taken together, dsDNA-specific mAb 2G8 revealed promising tumor-suppressive activity by inducing apoptosis, which provides a possible new strategy for the development of tumor intervening methods.
Cao
Qinghua
Q
Institute for ImmunoBiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
Xu
Wei
W
Wen
Zhenke
Z
Xu
Lin
L
Li
Kang
K
Chu
Yiwei
Y
Xiong
Sidong
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D019496:Cancer Vaccines / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000276:immunology*; D004273:DNA, Neoplasm / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D004273:DNA, Neoplasm; D004247:DNA