[The anti-lung cancer activity of a modified HPV 16 type mE6Δ/mE7 fusion protein based vaccine in an experimental animal model].
BACKGROUND
To investigate the outgrowth inhibition of the HPV16-positive murine lung tumor induced by a modified HPV16 mE6Δ/mE7 recombinant fusion protein vaccine in vivo and provide a new clue for the further immunotherapy.


METHODS
For prophylactic experiments, C57BL/6 mice were immunized with mE6Δ/mE7 fusion protein, and then inoculated with the TC-1 tumor cell, expressing HPV16 E6 and E7 viral proteins. On day 33 after inoculation, the tumor-free mice were re-challenged with a larger dose of TC-1 tumor cells. For therapeutic experiments, mice were vaccinated with mE6Δ/mE7 on days 3 and 14 after tumor cell inoculation. On day 60, the tumor-free mice were re-challenged with a larger dose of tumor cells. Tumor incidence and tumor volume of each group were calculated. MTT method was used to determine the proliferation of lymphocyte.


RESULTS
In the prophylactic experiments, immunization with the mE6Δ/mE7 completely protected the mice against the tumor cell challenge and rechallenge, and all the mice remained tumor free during the 100 days' observation period. In contrast, all the mice in PBS and IFA-treated groups developed tumors within 6-12 days after the first tumor cell inoculation, and died of tumor burden within 30 days. In the therapeutic experiments, the tumor formation rates were 20%, 90% and 60% in vaccinated, PBS and IFA groups respectively. In the next larger dose of tumor cells rechallenge experiment, 87.5% of vaccinated mice still remained tumor free, but all the mice from either PBS or IFA group developed tumors with 4-6 days. In addition, the results of MTT indicated that the proliferation of lymphocytes from vaccinated mice was stronger than that from control group.


CONCLUSIONS
The modified mE6Δ/mE7 can efficiently inhibit the growth of lung cancer in the animal model, indicating that mE6Δ/mE7 protein-based vaccine might show promise for the future clinical application.
Laboratory of Biochemistry and Molecular Biology, Cancer Hospital and Cancer Institute, Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100021, P.R.China.
Xiaoshan
X
Zhou
Qingzheng
Q
Zhao
Xinlai
X
Qian
Chunlei
C
Xu
Yuanzhi
Y
Lu