De-oncogenic HPV E6/E7 vaccine gets enhanced antigenicity and promotes tumoricidal synergy with cisplatin.
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.
Department of Anatomy and Histoembryology, Kunming Medical University, Kunming 650500, China.
Shaochun
S
Chen
Chaowei
C
Liao
Yiukay
Y
Lai
Yan
Y
Fan
Gang
G
Lu
Hua
H
Wang
Xiaoai
X
Zhang
Marie C M
MC
Lin
Shuilong
S
Leng
Hsiang-Fu
HF
Kung
D036002:ADP Ribose Transferases / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000627:therapeutic use*; D004357:Drug Synergism; D005098:Exotoxins / Q000627:therapeutic use; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000276:immunology / Q000627:therapeutic use*; D009856:Oncogene Proteins, Viral / Q000627:therapeutic use*; D050725:Papillomavirus E7 Proteins / Q000627:therapeutic use*; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D037521:Virulence Factors / Q000627:therapeutic use; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D019496:Cancer Vaccines; D002945:Cisplatin; D004268:DNA-Binding Proteins; D005098:Exotoxins; D015514:Oncogene Proteins, Fusion; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C052603:E6 protein, Human papillomavirus type 18; C059731:oncogene protein E7, Human papillomavirus type 16
cancer vaccine; cisplatin; papillomavirus E6 protein; papillomavirus E7 protein; uterine cervical neoplasms