An N-, C-terminally truncated basic fibroblast growth factor and LPD (liposome-polycation-DNA) complexes elicits a protective immune response against murine colon carcinoma.
Basic fibroblast growth factor (bFGF) is a mitogen for endothelial cells, which participates in tumor angiogenesis. Active immunity against bFGF could be a promising approach for the biotherapy of cancer. Because bFGF is abundant in normal and malignant tissues, it is presumably difficult for normal bFGF to induce immunity due to self-tolerance. In addition, previous studies have shown that a complex consisting of a cationic liposome and a non-coding plasmid DNA can be used to stimulate innate immunity. This stimulation initiates a potent cytokine response, which can inhibit tumor growth. To investigate the effects of immunity against bFGF on murine colon carcinomas, we employed an N-, C-terminally truncated basic fibroblast growth factor (tbFGF, of human origin) as an antigen and a liposome-DNA complex as an adjuvant. After six immunizations, a robust bFGF-specific immune response was elicited. Subsequently, inhibition of tumor growth and a significant reduction in tumor vasculature were observed. The antitumor effect was confirmed by adoptive therapy of activated spleen cells from the immunized mice. In vitro, a CTL assay revealed that bFGF-specific cytotoxic T lymphocytes (CTL) resulted in the lysis of mouse microvascular endothelial cells (MS1) rather than that of the CT26 colorectal cancer cells. These results suggest that anti-angiogenesis treatment induced by a bFGF-specific CTLs against microvascular endothelial cells may be a useful method for cancer therapy.
Zhang
Xiao-Ping
XP
State Key Laboratory of Biotherapy and Cancer Center, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Yang
Li
L
Shi
Hua-Shan
HS
Zhao
Xia
X
Deng
Hong-Xin
HX
Xiao
Wen-Jing
WJ
Mao
Yong-Qiu
YQ
Kan
Bing
B
Liu
Ya-Lin
YL
Zhang
Shuang
S
Li
Zhi-Mian
ZM
Zhang
Jing
J
Wei
Yu-Quan
YQ
D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics
D019496:Cancer Vaccines; D008081:Liposomes; D010446:Peptide Fragments; D016222:Fibroblast Growth Factor 2; D004247:DNA