Two-Arm Open-Labeled Trial of HPV-E6-Specific TCR-T Cells With or Without Anti-PD1 Auto-secreted Element in the Treatment of HPV-Positive Head and Neck Carcinoma or Cervical Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- To Determine the Maximum Tolerated Dose
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Expected to live longer than 12 weeks
- •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
Exclusion Criteria
- •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
Arms & Interventions
HPV TCR-T with anti-PD1
HPV E6-specific TCR-T cell with anti-PD1 auto-secreted element
Intervention: HPV E6-specific TCR-T cells (Drug)
HPV TCR-T
HPV E6-specific TCR-T cell
Intervention: HPV E6-specific TCR-T cells (Drug)
Outcomes
Primary Outcomes
To Determine the Maximum Tolerated Dose
Time Frame: 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 Outcomes
No secondary outcomes reported
Investigators
Qingzhu Jia, M.D.
Secretary of Research
Xinqiao Hospital of Chongqing