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Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7
1Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Abstract:
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-1) that demonstrated significant anti-tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/ LAMP-1 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 10(6) TC-1 cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/ LAMP-1 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-1 cells and then vaccinated with Sig/E7/ LAMP-1. Treatment with Sig/E7/LAMP-1 was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP-1 resulted in regression of fully established lung tumors in 10% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP-1 vaccine is effective in controlling the hematogenous spread of TC-1 tumor cells. In addition, the TC-1 lung metastasis model can be used to test the efficacy of various E6/E7-specific vaccines and immunotherapeutic strategies.
Insights
The Sig/E7/LAMP-1 vaccine shows promise in preventing and treating metastatic tumors. This cancer immunotherapy strategy effectively controlled tumor spread in a mouse model, offering new hope for metastasis treatment.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Cancer immunotherapy aims to prevent and treat tumor metastasis.
- A previously developed recombinant vaccinia-based vaccine, Sig/E7/LAMP-1, showed anti-tumor effects in a subcutaneous model.
- The efficacy of this vaccine against metastatic tumors required further investigation.
Purpose of the Study:
- To evaluate the Sig/E7/LAMP-1 vaccine's potency in preventing and treating metastatic tumors.
- To establish and utilize a lung metastasis model for assessing anti-metastatic vaccine efficacy.
Main Methods:
- A lung metastasis model was generated using human papillomavirus type 16 (HPV-16) E6/E7 expressing TC-1 tumor cells injected intravenously into C57BL/6 mice.
- In vivo tumor prevention experiments involved vaccinating mice with Sig/E7/LAMP-1 before tumor cell challenge.
- In vivo treatment experiments involved vaccinating mice after tumor cell inoculation to assess efficacy against established tumors.
Main Results:
- In prevention studies, 80% (8/10) of vaccinated mice remained tumor-free compared to 0% in controls.
- In treatment studies, Sig/E7/LAMP-1 eliminated preexisting tumor cells in 4/5 mice.
- Established lung tumors showed regression in 10% (5/10) of vaccinated mice.
Conclusions:
- The Sig/E7/LAMP-1 vaccine is effective in controlling the hematogenous spread of TC-1 tumor cells.
- The TC-1 lung metastasis model serves as a valuable platform for testing E6/E7-specific vaccines and immunotherapies.