TY - JOUR
T1 - Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein
AU - Ji, Hongxiu
AU - Chang, Edwin Y.
AU - Lin, Ken Yu
AU - Kurman, Robert J.
AU - Pardoll, Drew M.
AU - Wu, T. C.
PY - 1998
Y1 - 1998
N2 - An important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported a recombinant vaccinia-based vaccine (Sig/E7/LAMP-I) that demonstrated significant anti-tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/LAMP-I vaccine in preventing and treating metastatic tumors. A tumor metastasis model was generated by injecting human papillomavirus type 16 (HPV-16) E6/E7 expressing tumor cells, designated TC- 1, into the tail vein of syngeneic C57BL/6 mice. All the naive mice injected with 1 x 106 TC-I cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/LAMP-I followed by tumor challenge. While tumor growth was observed in all of the mice (10/10) in the control groups, 8 of 10 vaccinated mice (80%) remained tumor-free 2 months post-tumor challenge. For in vivo treatment experiments, mice were first inoculated with TC-I cells and then vaccinated with Sig/E7/LAMP-I. Treatment with Sig/E7/LAMP-I was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP-I resulted in regression of fully established lung tumors in 50% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP-I vaccine is effective in controlling the hematogenous spread of TC-I tumor cells. In addition, the TC-I lung metastasis model can be used to test the efficacy of various E6/E7-specific vaccines and immunotherapeutic strategies.
AB - An important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported a recombinant vaccinia-based vaccine (Sig/E7/LAMP-I) that demonstrated significant anti-tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/LAMP-I vaccine in preventing and treating metastatic tumors. A tumor metastasis model was generated by injecting human papillomavirus type 16 (HPV-16) E6/E7 expressing tumor cells, designated TC- 1, into the tail vein of syngeneic C57BL/6 mice. All the naive mice injected with 1 x 106 TC-I cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/LAMP-I followed by tumor challenge. While tumor growth was observed in all of the mice (10/10) in the control groups, 8 of 10 vaccinated mice (80%) remained tumor-free 2 months post-tumor challenge. For in vivo treatment experiments, mice were first inoculated with TC-I cells and then vaccinated with Sig/E7/LAMP-I. Treatment with Sig/E7/LAMP-I was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP-I resulted in regression of fully established lung tumors in 50% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP-I vaccine is effective in controlling the hematogenous spread of TC-I tumor cells. In addition, the TC-I lung metastasis model can be used to test the efficacy of various E6/E7-specific vaccines and immunotherapeutic strategies.
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U2 - 10.1002/(SICI)1097-0215(19980925)78:1<41::AID-IJC8>3.0.CO;2-X
DO - 10.1002/(SICI)1097-0215(19980925)78:1<41::AID-IJC8>3.0.CO;2-X
M3 - Article
C2 - 9724092
AN - SCOPUS:0031846264
SN - 0020-7136
VL - 78
SP - 41
EP - 45
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -