HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Head and Neck Squamous Cell Carcinoma, Cervical Cancer

Intervention / Treatment
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* Drug: HPV E6-specific TCR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV TCR-T<br>HPV E6-specific TCR-T cell | Drug: HPV E6-specific TCR-T cells<br>* Patients were infused with HPV E6-specific TCR-T cells<br>|
| Experimental: HPV TCR-T with anti-PD1<br>HPV E6-specific TCR-T cell with anti-PD1 auto-secreted element | Drug: HPV E6-specific TCR-T cells<br>* Patients were infused with HPV E6-specific TCR-T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Maximum Tolerated Dose | 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 | 8 weeks |