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

Phase 1
Recruiting
Conditions
Nasopharyngeal Carcinoma
Interventions
Drug: EBV-specific TCR-T cell with cytokine auto-secreting element
Registration Number
NCT04509726
Lead Sponsor
Xinqiao Hospital of Chongqing
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
20
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
EBV TCR-TEBV-specific TCR-T cell with cytokine auto-secreting element-
Primary Outcome Measures
NameTimeMethod
The Maximum Tolerated Dose8 weeks

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Department of Oncology, Xinqiao Hospital

🇨🇳

ChongQing, Chongqing, China

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