Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer
Cervical cancer caused by human papillomavirus (HPV) infections is the fourth most common cancer in women worldwide. Current prophylactic HPV vaccines have achieved promising success in preventing HPV infection. However, still 570,000 new cases were reported in 2018. The current primary treatment fo...
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doaj-fbf85183bf8543acb09494b17c66a56a2021-06-24T06:35:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.678318678318Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical CancerBilian Huang0Linjing Zhu1Hongxia Wei2Haixia Shi3Doudou Zhang4Huanyun Yuan5Linlin Luan6Nan Zheng7Shijie Xu8Waqas Nawaz9Ying Hong10Xilin Wu11Xilin Wu12Zhiwei Wu13Zhiwei Wu14Zhiwei Wu15Zhiwei Wu16Center for Public Health Research, Medical School, Nanjing University, Nanjing, ChinaDepartment of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, ChinaDepartment of Infection, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Antibody, Y-Clone Medical Science Co. Ltd., Suzhou, ChinaDepartment of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, ChinaDepartment of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, ChinaDepartment of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, ChinaCenter for Public Health Research, Medical School, Nanjing University, Nanjing, ChinaDepartment of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, ChinaCenter for Public Health Research, Medical School, Nanjing University, Nanjing, ChinaObstetrics and Gynecology Department, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, ChinaCenter for Public Health Research, Medical School, Nanjing University, Nanjing, ChinaDepartment of Antibody, Abrev Biotechnology Co., Ltd., Nanjing, ChinaCenter for Public Health Research, Medical School, Nanjing University, Nanjing, ChinaSchool of Life Sciences, Ningxia University, Yinchuan, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, ChinaState Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, ChinaCervical cancer caused by human papillomavirus (HPV) infections is the fourth most common cancer in women worldwide. Current prophylactic HPV vaccines have achieved promising success in preventing HPV infection. However, still 570,000 new cases were reported in 2018. The current primary treatment for the patient with cervical cancer is either surgery or chemoradiotherapy. Cervical cancer still lacks standard medical therapy. HPV18 induced cervical cancer has the worst prognosis and high mortality compared to other HPV infections. The development of HPV18 related with cervical malignancy requires the persistent infection of cervical–vaginal epithelium by HPV18 subtype, which can take years to transform the epithelium. This period of repeated infection provides a window for therapeutic intervention. Neutralizing antibodies formulated as topical agents that inhibit HPV18 infection should reduce the chance of cervical malignancy. We previously demonstrated that potent neutralizing anti-sera against HPV18 infection were induced by HPV18 viral like particle (VLP) generated in mammalian cells. We, therefore, isolated two potent neutralizing antibodies, 2A12 and 8H4, from over 3,810 hybridomas prepared from mice immunized with HPV18 VLP. 2A12 and 8H4 exhibited excellent potency, with 50% virus-inhibitory concentrations (IC50) of 0.4 and 0.9 ng/ml, respectively. Furthermore, 2A12 and 8H4 recognized distinct and non-overlapping quaternary epitopes and bound specifically with HPV18. Humanized 2A12 (Hu2A12) retained comparable neutralizing activity against HPV18 infection in various acidic pH settings and in hydrogel formulation with IC50 values of 0.04 to 0.77 ng/ml, indicating that Hu2A12 will be a promising candidate for clinical development as a topical vaginal biopharmaceutical agent against HPV18 infection.https://www.frontiersin.org/articles/10.3389/fimmu.2021.678318/fullHPV18cervical cancerneutralizing antibodiestopical agentshumanized antibody |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bilian Huang Linjing Zhu Hongxia Wei Haixia Shi Doudou Zhang Huanyun Yuan Linlin Luan Nan Zheng Shijie Xu Waqas Nawaz Ying Hong Xilin Wu Xilin Wu Zhiwei Wu Zhiwei Wu Zhiwei Wu Zhiwei Wu |
spellingShingle |
Bilian Huang Linjing Zhu Hongxia Wei Haixia Shi Doudou Zhang Huanyun Yuan Linlin Luan Nan Zheng Shijie Xu Waqas Nawaz Ying Hong Xilin Wu Xilin Wu Zhiwei Wu Zhiwei Wu Zhiwei Wu Zhiwei Wu Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer Frontiers in Immunology HPV18 cervical cancer neutralizing antibodies topical agents humanized antibody |
author_facet |
Bilian Huang Linjing Zhu Hongxia Wei Haixia Shi Doudou Zhang Huanyun Yuan Linlin Luan Nan Zheng Shijie Xu Waqas Nawaz Ying Hong Xilin Wu Xilin Wu Zhiwei Wu Zhiwei Wu Zhiwei Wu Zhiwei Wu |
author_sort |
Bilian Huang |
title |
Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer |
title_short |
Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer |
title_full |
Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer |
title_fullStr |
Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer |
title_full_unstemmed |
Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer |
title_sort |
potent neutralizing humanized antibody with topical therapeutic potential against hpv18-related cervical cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-06-01 |
description |
Cervical cancer caused by human papillomavirus (HPV) infections is the fourth most common cancer in women worldwide. Current prophylactic HPV vaccines have achieved promising success in preventing HPV infection. However, still 570,000 new cases were reported in 2018. The current primary treatment for the patient with cervical cancer is either surgery or chemoradiotherapy. Cervical cancer still lacks standard medical therapy. HPV18 induced cervical cancer has the worst prognosis and high mortality compared to other HPV infections. The development of HPV18 related with cervical malignancy requires the persistent infection of cervical–vaginal epithelium by HPV18 subtype, which can take years to transform the epithelium. This period of repeated infection provides a window for therapeutic intervention. Neutralizing antibodies formulated as topical agents that inhibit HPV18 infection should reduce the chance of cervical malignancy. We previously demonstrated that potent neutralizing anti-sera against HPV18 infection were induced by HPV18 viral like particle (VLP) generated in mammalian cells. We, therefore, isolated two potent neutralizing antibodies, 2A12 and 8H4, from over 3,810 hybridomas prepared from mice immunized with HPV18 VLP. 2A12 and 8H4 exhibited excellent potency, with 50% virus-inhibitory concentrations (IC50) of 0.4 and 0.9 ng/ml, respectively. Furthermore, 2A12 and 8H4 recognized distinct and non-overlapping quaternary epitopes and bound specifically with HPV18. Humanized 2A12 (Hu2A12) retained comparable neutralizing activity against HPV18 infection in various acidic pH settings and in hydrogel formulation with IC50 values of 0.04 to 0.77 ng/ml, indicating that Hu2A12 will be a promising candidate for clinical development as a topical vaginal biopharmaceutical agent against HPV18 infection. |
topic |
HPV18 cervical cancer neutralizing antibodies topical agents humanized antibody |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.678318/full |
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