[Enhanced inhibitory effect of MUC1 gene vaccine on breast cancer growth by GM-CSF].
OBJECTIVE
To investigate if GM-CSF adjuvant could enhance the inhibitory effect of the MUC1 gene vaccine on EMT6 breast cancer growth.


METHODS
Female BALB/c mice were immunized intramuscularly with 100 microgram MUC1 gene vaccine 3 times at 3 week intervals. On 1, 3 and 5 days after intramuscular immunization, GM-CSF 100 microL(1 microg/100 microL) was given s.c. respectively. Three weeks after the last immunization, tumor challenge experiments were performed by using MUC1 expressing tumor cell line EMT6. Tumor growth inhibition was observed two weeks later. After 43 d of challenge experiments, all mice were killed and tumors were weighted. CTL-specific cytotoxicity was detected by (51)Cr release assay.


RESULTS
After 43 d of challenge experiments, the size of EMT6 tumor in MUC1 DNA+GM-CSF, MUC1 DNA, pcDNA3.1(+)+GM-CSF and pcDNA3.1(+) group were (135+/-33.8) mm(3), (250+/-34.3) mm(3), (568+/-43.6) mm(3) and (596+/-48.2) mm(3), respectively. The average weight (g) of EMT6 tumors in those four groups were 0.81+/-0.42, 1.23+/-0.41, 2.30+/-0.48 and 2.28+/-0.58, respectively. EMT6 breast cancer growth in mice of MUC1 gene vaccine group was suppressed significantly(P<0.05), compared with that in pcDNA3.1(+) control group. Co-delivery of GM-CSF adjuvant and MUC1 DNA immunization enhanced the antitumour effects(P<0.05). The cytotoxicity of MUC1-specific CTLs to EMT6 target cells was different at various ratios of effector cells to target cells. At ratios of 100:1, 50:1, 25:1 and 12.5:1, the specific lysis for MUC1 DNA+GM-CSF group reached 68.5%, 53.4%, 35.9% and 28.5%, MUC1 cDNA group 54.1%, 39.8%, 26.4% and 20.1%, while for control groups 13.2%, 10%, 8.2%, 7.2% and 11.7%, 9.8%, 7.7%, 7.0%, respectively. GM-CSF enhanced the cytotoxicity of CTL induced by MUC1 DNA immunization(P<0.05).


CONCLUSIONS
GM-CSF adjuvant significantly enhanced the inhibitory effect of the MUC1 gene vaccine on EMT6 breast cancer growth.
Yuan
Shi-fang
SF
Department of Vascular and Endocrine Surgery, Fourth Military Medical University, Xi'an 710032, China. shifangy@fmmu.edu.cn
Li
Kai-zong
KZ
Wang
Ling
L
Yan
Zhen
Z
Han
Wei
W
Zhang
Ying-qi
YQ
D000818:Animals; D000951:Antigens, Neoplasm; D019556:COS Cells; D019496:Cancer Vaccines / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1; D009077:Mucins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D014162:Transfection
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor