Trials / Recruiting
RecruitingNCT06156150
The Role of B7-H4 in Tumor Vaccine
The Role and Mechanism of B7-H4/ATF3 Axis From Glioma Associated Macrophages in Treatment Resistance of Cancer Vaccine
- Status
- Recruiting
- Phase
- —
- Study type
- Observational
- Enrollment
- 160 (estimated)
- Sponsor
- Huashan Hospital · Academic / Other
- Sex
- All
- Age
- 18 Years – 80 Years
- Healthy volunteers
- Not accepted
Summary
Glioma patients have poor prognosis because of limited choices of treatment. Therapeutic cancer vaccines have been proved to improve survival in glioma, but resistance is a new challenge for vaccine treatment, and the mechanism is unclear. The applicant found in previous papers that glioma cells induced B7-H4 overexpression in macrophages, and the expression level of B7-H4 is highly correlated with vaccine resistance. Preliminary experiments indicated that B7-H4 protein in macrophages inhibited the expression of ATF3, STAT1 and CXCL9/10, which also resulted in decreased T cell infiltration in glioma model of mouse and was a negative factor of vaccine benefits. Therefore, the applicant hypothesize that B7-H4 inhibits STAT1 transcription by reducing expression of ATF3, resulting in decreased phosphorylated-STAT1 in nucleus, which inhibiting expression and secretion of chemokines 9/10. Thereby, reduced infiltration of T cells in microenvironment will be followed, which ultimately promotes resistance of vaccine treatment in glioma. The follow-up plan of this project will be conducted based on the cells, organoid platform and animal experiments to confirm the role and mechanism of macrophage-derived B7-H4 in secretion of chemokines for T cells and treatment resistance of vaccines. Moreover, the DC vaccine produced by team of the applicant will be used to assess the probability of reversing vaccine resistance when intervening B7-H4 axis. Finally, a model for evaluating clinical benefits from vaccine will be established based on data from clinical trials combining with expression of B7-H4 and clinicopathologic features. This study will provide new evidences for the treatment of cancer vaccines in gliomas.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | tumor vaccine | DC vaccine produced by the Team |
Timeline
- Start date
- 2023-11-26
- Primary completion
- 2026-12-31
- Completion
- 2026-12-31
- First posted
- 2023-12-05
- Last updated
- 2023-12-05
Locations
1 site across 1 country: China
Source: ClinicalTrials.gov record NCT06156150. Inclusion in this directory is not an endorsement.