The Role of B7-H4 in Tumor Vaccine

NCT06156150 | Recruiting

• 2 other identifiers: KY2023-9978230162487
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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

Glioma

Keywords

glioma; treatment resistance; immunotherapy; cancer vaccine; macrophage

Outcome Measures

Primary Outcomes (1)

• IHC analysis

  Different expression level of proteins (CD3,CD8,B7-H4 et.ac) in Gliomas with different grades and molecular subgroups (100 cases) will be measured using immunohistochemical.

  36 months

Secondary Outcomes (5)

• Transcriptomics

  36 months

• Immunomics

  36 months

• Proteomics

  36 months

• Radiomics

  36 months

• Genomics

  36 months

Study Arms (2)

glioma patients receiving conventional treatment

surgery+radiotherapy+chemotherapy

glioma patients with tumor vaccine

surgery+radiotherapy+chemotherapy+tumor vaccine

Biological: tumor vaccine

Interventions

tumor vaccine BIOLOGICAL

DC vaccine produced by the Team

glioma patients with tumor vaccine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing glioma surgery at Huashan Hospital

You may qualify if:

• The patients with glioma in the Department of Neurosurgery of Huashan Hospital Affiliated to Fudan University who meet the following three conditions can be enrolled
• They were 18-80 years old, male and female;
• The pathological results of frozen section during operation were gliomas;
• Tissue (6 mm \* 6 mm) can be used for cell sorting on the basis of not affecting clinical routine diagnosis;
• Sign informed consent.

You may not qualify if:

• Patients who meet any of the following criteria will not be included in this study:
• Participants in other clinical trials;
• Pregnant women.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Di Chen

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

Cancer Vaccines

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 26, 2023
• First Posted: December 5, 2023
• Study Start: November 26, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 5, 2023

Record last verified: 2023-11

Locations

CN (1)