Cervical Intraepithelial Neoplasia
Conditions
Keywords
Cervical Intraepithelial Neoplasia, Human Papillomavirus, Dentritic Vaccine, E6/E7 protein
Brief summary
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.
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.
Interventions
BIOLOGICALVaccinated 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.
Sponsors
Shenzhen People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety] | 3 months after the last vaccination injection | 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. |
| Immunogenicity of neoantigen-primed DC Vaccines | once per three month | Immunogenicity of the DC vaccine will be measured to detect changes of neoantigen-specific T cells by flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | once per three month | Objective Response Rate will be measured by detection of protein expression of HPV E6 / E7and evaluation of CIN phase |
Countries
China
Contacts
Primary ContactLili Ren, Ph.D.
Backup ContactFanli Meng, Ph.D.
Outcome results
None listed