EBV Specific Cytokine Secreting TCR-T Cells in the Treatment of EBV-Positive Metastatic/Refractory Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Epstein-Barr virus (EBV) infections is known to be a high-risk factor to induce cervical cancers. To date, EBV-related nasopharyngeal carcinoma (NPC) is still a major concern in east Asia, especially in China. Concurrent therapies for NPC have limited response rate and high chance of relapse. However, EBV-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 EBV-epitope 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. Cytokine seemed to represent the ideal candidate for tumor immunotherapy, due to its ability to activate both innate (NK cells) and adaptive immunities. therefore, TCR-T cells armed with a cytokine -secretion element could further enhance the efficacy of TCR-T in solid cancers.

Official Title
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Single-Arm Trial of EBV Specific Cytokine Secreting TCR-T Cells in the Treatment of EBV-Positive Head and Neck Carcinoma Metastatic/Refractory Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: EBV-specific TCR-T cell with cytokine auto-secreting element


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 EBV positive NPC, 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBV TCR-T<br> | Drug: EBV-specific TCR-T cell with cytokine auto-secreting element<br>* Patients were pre-conditioned with chemotherapy and infused with EBV-specific TCR-T cells with cytokine auto-secreting element<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Maximum Tolerated Dose | Verify the MTD of TCR-T cells for EBV antigen for treatment. The first nine patients enrolled in this project will be infused in a dose-escalation approach. The first group of patients will receive 5e+6/kg TCR-T cells, the second group will receive 1e+7/kg TCR-T cells, and the third group will receive 5e+7/kg TCR-T cells. The remaining 11 patients will be infused with TCR-Ts in the maximum tolerated dose. | 8 weeks |