DC Vaccines Targeting HPV16/18 E6/E7 Protein to Regress CINI/CIN2

Clinical Study on the Regress of Cervical Intraepithelial Neoplastic(CIN) 1/CIN2 by Highly Effective DC Vaccines Targeting HPV E6/ E7 Protein

To establish therapeutic dendritic cell (DC) vaccines targeting HPV 16/18 E6/E7 protein to block the progression of CIN1/CIN2 to cervical cancer and evaluate the safety and efficacy of the vaccines.

Study Overview

• Status: Unknown
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Biological: Vaccinated group

Detailed Description

Cervical cancer is the second most common cause of cancer-related deaths among women worldwide with 10000 new cases each year in China. The high-risk human papillomavirus (HPV) was the major cause of cervical cancer. The oncoproteins E6 and E7 encoded by HPV16 and 18, are consistently expressed in HPV-associated Cervical cancer and are responsible for the cervical cancer malignant progression. Targeting the E6/E7 proteins could be very helpful to regress the CIN 1/2 and block the tumorigenesis.

By this research, we aim to establish the HPV16/18 E6/E7 peptide library which could induce the strong anti-virus immune response and to vaccinate the CIN 1/2 patients with dendritic cell vaccines loaded HPV 16/18 E6/E7 epitopes.

Including:

1. To create an effective HPV 16/18 E6/E7 antigen peptide library using NetMHCspan software based on the MHC-I subtype of the Chinese population and screen E6/E7protein peptides with high binding affinity to MHC molecules;
2. To develop HPV 16/18 E6/E7- pulsed DC vaccines and evaluate the safety and efficacy of DC vaccines;
3. The patients are vaccinated with the HPV16/18 E6/E7- pulsed DC vaccines
4. To evaluate the safety and efficacy of DC vaccines loaded with HPV 16/18 E6/E7.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518020
      • Shenzhen People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age ≥18 years ≤ 70 years at the time of informed consent
2. HPV type 16/18 positive
3. Pathologically confirmed CIN1/2 and no other cervical disease
4. adequate organ functions.

Exclusion Criteria:

1. Severe allergy to drugs
2. Women of child-bearing potential who are pregnant or breast-feeding
3. Any form of primary immunodeficiency
4. With serious cardiac, cerebrovascular and primary diseases
5. With a history of severe mental illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccinated group; Patients will be vaccinated with autologous mature dendritic cells-loaded with HPV 16/18 E6/E7, DC vaccine will be injected into the adjacent lymph-node 6 times, once a week.	Biological: Vaccinated group; Develop highly reactive DC vaccines targeting HPV 16/18 E6/ E7 protein and DC vaccine would be injected to patients once a week, six doses in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety]	Safety of personalized neoantigen vaccine will be measured by the number of subjects experiencing each type of adverse event. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.	3 months after the last vaccination injection
Immunogenicity of neoantigen-primed DC Vaccines	Immunogenicity of the DC vaccine will be measured to detect changes of neoantigen-specific T cells by flow cytometry.	once per three month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective Response Rate will be measured by detection of protein expression of HPV E6 / E7and evaluation of CIN phase	once per three month

Collaborators and Investigators

• Sponsor: Shenzhen People's Hospital
• Investigators: Study Director: Hui Qi, M.D., Shen Zhen People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2019
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Cervical Intraepithelial Neoplasia; Human Papillomavirus; Dentritic Vaccine; E6/E7 protein
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma in Situ; Neoplasms; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: ShenzhenPH BTR-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No