In order to develop more effective therapeutic
vaccines against
cancers with high-risk human papillomavirus (HPV)
infection, it is crucial to enhance the immunogenicity, eliminate the oncogenicity of
oncoproteins, and take a combination of E7- and E6-containing
vaccines. It has been shown recently that PE(ΔIII)-E7-KDEL3 (E7), a fusion
protein containing the HPV16
oncoprotein E7 and the translocation domain of
Pseudomonas aeruginosa exotoxin A, is effective against TC-1
tumor cells inoculated in mice, therefore, we engineered PE(ΔIII)-E6-CRL-KDEL3 (E6), the de-oncogenic versions of the E7 and E6 fusion
proteins [i.e. PE(ΔIII)-E7(d)-KDEL3, E7(d), and PE(ΔIII)-E6(d)-CRL-KDEL3, E6(d)] and tested the immunoefficacies of these fusion
proteins as mono- and
bivalent vaccines. Results indicated that the E7(d) get higher immunogenicity than its wild type and the E6 fusion
proteins augmented the immunogenicity and antitumor effects of their E7 counterparts. Furthermore, the
bivalent vaccine system E7(d) plus E6(d), in the presence of
cisplatin, showed the best tumoristatic and tumoricidal effects against established
tumors in vivo. Therefore, it can be concluded that this novel therapeutic
vaccine system, upon further optimization, may shed new light on clinical management of HPV-related
carcinomas.