Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
Epstein-Barr virus (EBV) infections is known to be a high-risk factor to induce nasopharyngeal cancers. To date, EBV-related head and neck squamous cell carcinoma (HNSCC) is still a major concern in east Asia, especially in China. Concurrent therapies for HNSCC 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 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.
Interventions
DRUGEBV-specific TCR-T cell with anti-PD1 auto-secreted element
Patients were pre-conditioned with chemotherapy and infused with EBV-specific TCR-T cells with anti-PD1 auto-secreted element
Sponsors
Xinqiao Hospital of Chongqing
TCRCure Biopharma Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Expected to live longer than 12 weeks * PS 0-2 * Pathology confirmed as EBV positive HNSCC, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Tolerated Dose | 8 weeks | Verify the MTD of TCR-T cells for EBV antigen for treatment. 18 patients will be enrolled in this project, using a dose-escalation approach. The first group of patients will receive 5x10e6/kg TCR-T cells, the second group will receive 1x10e7/kg TCR-T cells, the third group will receive 5x10e7/kg TCR-T cells, the forth group will receive 1x10e8/kg. After confirmation of safety for 5×10e7 dose group, we then added IL-2 on this dose level for consecutive 6 patients. The remaining 6 pts are for enrollment of 1×10e8/kg dose level. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORBo Zhu, MD, PhD
Army Medical University, China
Outcome results
None listed