HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer
- Conditions
- Head and Neck Squamous Cell CarcinomaCervical Cancer
- Interventions
- Registration Number
- NCT03578406
- Lead Sponsor
- Xinqiao Hospital of Chongqing
- Brief Summary
Human papillomavirus infections 16 (HPV16) is known to be a high-risk factor to induce cervical cancers. To date, HPV16-related cervical cancer is still a major concern in developing countries where vaccination is not prevalent. Concurrent therapies for cervical cancers have limited response rate and high chance of relapse. However, HPV16-induced cancers provided an ideal target for T cell-based immunotherapy due to the non-self origins. Engineered T cells bearing a TCR (TCR-T) that can specifically recognize the presented HPV antigen become a viable approach to treat this type of cancer. Though engineered T therapies have been well-recognized in hematological cancers, solid cancer treatment has been a major hurdle due to the immune-suppressive tumor microenvironment. One key mechanism of tumor-elicited suppression is the PDL1-PD1 interaction which induces T cell exhaustion. Therefore, TCR-T cells armed with a PD1 antagonist could further enhance the efficacy of TCR-T in solid cancers.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 20
- Expected to live longer than 12 weeks
- PS 0-2
- Pathology confirmed as HPV16 positive malignant tumor, either metastatic or recurrent disease
- Creatinine <2.5mg/dl
- ALT/AST is lower than three times ULN.
- No contraindications of leukocyte collection
- Before entering the trial, women must adopt a reliable method of contraception until 30 days after infusion.
- Understand this trial and have signed an informed consent
- Patients with symptomatic brain metastasis
- With other uncontrolled malignant tumors.
- Hepatitis B or Hepatitis C activity period, HIV infected patients
- Any other uncontrolled disease that interferes with the trial
- Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis and cerebral hemorrhage
- Untreated hypertension or hypertensive patients
- A person with a history of mental illness that is difficult to control
- Researchers do not consider it appropriate to participate in this trial
- Patients who have been using immunosuppressive agents for a long time after organ transplants, except for recent or current inhaled corticosteroids
- Subjects who have been pregnant or nursing, or who plan for pregnancy within 2 months of treatment or after the end of treatment
- An illness affects a person who signs a written consent or complies with a study procedure, or who is unwilling or unable to comply with the research requirements
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HPV TCR-T HPV E6-specific TCR-T cells HPV E6-specific TCR-T cell HPV TCR-T with anti-PD1 HPV E6-specific TCR-T cells HPV E6-specific TCR-T cell with anti-PD1 auto-secreted element
- Primary Outcome Measures
Name Time Method To Determine the Maximum Tolerated Dose 8 weeks Verify the MTD of TCR-T cells for HPV16 E6 antigen for treatment. Nine patients will be enrolled in this project, using a dose-climbing approach, with every three patients as a group. The first group of patients returned to 5x106/kg TCR-T cells, the second group returned to 1x107/kg TCR-T cells, and the third group returned to 5x107/kg TCR-T cells
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Qingzhu Jia
🇨🇳Chongqing, Chongqing, China