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

NCT03578406 | Completed Phase 1 DMC

• 1 other identifier: XQDC20180520
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Head and Neck Squamous Cell Carcinoma; Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

HPV TCR-T

EXPERIMENTAL

HPV E6-specific TCR-T cell

Drug: HPV E6-specific TCR-T cells

Interventions

HPV E6-specific TCR-T cells DRUG

Patients were infused with HPV E6-specific TCR-T cells

HPV TCR-T

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• TCRCure Biopharma Ltd.: collaborator
• Xinqiao Hospital of Chongqing: lead

Study Sites (1)

Qingzhu Jia

Chongqing, Chongqing Municipality, 400037, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Study Officials

• Bo Zhu

  Oncology of Department, Xinqiao Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Secretary of Research

Study Record Dates

• First Submitted: May 28, 2018
• First Posted: July 6, 2018
• Study Start: September 1, 2018
• Primary Completion: April 30, 2022
• Study Completion: October 30, 2022
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

CN (1)