Monoclonal Antibodies Against Human Papillomavirus E6 and E7 Oncoproteins Inhibit Tumor Growth in Experimental Cervical Cancer

Zewei Jiang, Joseph Albanese, Joshua Kesterson, Joshua Warrick, Rouzan G. Karabakhtsian, Ekaterina Dadachova, Rébécca Phaëton

Research output: Contribution to journalArticle

Abstract

Nearly all cases of cervical cancer are initiated by persistent infection with high-risk strains of human papillomavirus (hr-HPV). When hr-HPV integrates into the host genome, the constitutive expression of oncogenic HPV proteins E6 and E7 function to disrupt p53 and retinoblastoma regulation of cell cycle, respectively, to favor malignant transformation. HPV E6 and E7 are oncogenes found in over 99% of cervical cancer, they are also expressed in pre-neoplastic stages making these viral oncoproteins attractive therapeutic targets. Monoclonal antibodies (mAbs) represent a novel potential approach against the actions of hr-HPV E6 and E7 oncoproteins. In this report, we describe the utilization of anti-HPV E6 and HPV E7 mAbs in an experimental murine model of human cervical cancer tumors. We used differential dosing strategies of mAbs C1P5 (anti-HPV 16 E6) and TVG701Y (anti-HPV E7) administered via intraperitoneal or intratumoral injections. We compared mAbs to the action of chemotherapeutic agent Cisplatin and demonstrated the capacity of mAbs to significantly inhibit tumor growth. Furthermore, we investigated the contribution of the immune system and found increased complement deposition in both C1P5 and TVG701Y treated tumors compared to irrelevant mAb therapy. Taken together, the results suggest that anti-HPV E6 and E7 mAbs exert inhibition of tumor growth in a viral-specific manner and stimulate an immune response that could be exploited for an additional treatment options for patients.

Original languageEnglish (US)
Pages (from-to)1289-1295
Number of pages7
JournalTranslational Oncology
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2019

Fingerprint

Oncogene Proteins
Uterine Cervical Neoplasms
Monoclonal Antibodies
Growth
Neoplasms
Human papillomavirus 16
Retinoblastoma
Oncogenes
Cisplatin
Immune System
Cell Cycle
Theoretical Models
Therapeutics
Genome
Injections
Infection
Proteins

Keywords

  • cervical cancer
  • HPV E6 and E7
  • immunotherapy
  • monoclonal antibodies
  • nude mice

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Monoclonal Antibodies Against Human Papillomavirus E6 and E7 Oncoproteins Inhibit Tumor Growth in Experimental Cervical Cancer. / Jiang, Zewei; Albanese, Joseph; Kesterson, Joshua; Warrick, Joshua; Karabakhtsian, Rouzan G.; Dadachova, Ekaterina; Phaëton, Rébécca.

In: Translational Oncology, Vol. 12, No. 10, 01.10.2019, p. 1289-1295.

Research output: Contribution to journalArticle

Jiang, Zewei ; Albanese, Joseph ; Kesterson, Joshua ; Warrick, Joshua ; Karabakhtsian, Rouzan G. ; Dadachova, Ekaterina ; Phaëton, Rébécca. / Monoclonal Antibodies Against Human Papillomavirus E6 and E7 Oncoproteins Inhibit Tumor Growth in Experimental Cervical Cancer. In: Translational Oncology. 2019 ; Vol. 12, No. 10. pp. 1289-1295.
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