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Multiple therapeutic peptide vaccines for patients with advanced gastric cancer
Yoshiyuki Fujiwara1, Kaoru Okada2, Takeshi Omori2
1Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
Abstract:
We performed a clinical trial using HLA-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides for advanced gastric cancer (GC). Thirty-five GC patients who had shown resistance to the standard therapy were enrolled in this clinical trial using vaccinations with a mixture of multiple peptides derived from DEPDC1, URLC10, FoxM1, Kif20A and VEGFR1. The safety, the overall survival (OS), and the immunological responses based on an ELISPOT assay were determined to assess differences in patients who were HLA-A24-positive [24(+)] and HLA-A24-negative [24(-)]. No severe adverse effects were observed except for severe skin reactions in 4 patients. The differences in OS were not significant between patients who were 24(+) and 24(-). In the 24(+) group, patients who showed T cell responses specific to antigen peptides had a tendency towards better survival than those who showed no response, especially to the DEPDC1 peptide. The patients with local skin reactions had significantly better OS than the others. Peptide vaccine therapy was found to be safe and is expected to induce specific T cell responses in patients with advanced GC. The survival benefit of peptide vaccine monotherapy may not have been shown and further trials are needed to confirm these results.
Insights
This study evaluated peptide vaccines for advanced gastric cancer (GC). While safe and inducing T-cell responses, the therapy did not significantly improve overall survival, necessitating further trials.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Advanced gastric cancer (GC) often shows resistance to standard therapies.
- Novel therapeutic strategies, including peptide vaccines targeting cancer-testis antigens and anti-angiogenic peptides, are under investigation for GC.
- Human Leukocyte Antigen (HLA)-A24 is a significant factor in immune responses to cancer vaccines.
Purpose of the Study:
- To assess the safety and efficacy of a novel peptide vaccine in patients with advanced gastric cancer.
- To evaluate the immunological responses and overall survival (OS) in relation to HLA-A24 status.
- To explore the correlation between specific peptide responses, adverse events, and patient survival.
Main Methods:
- A clinical trial involving 35 advanced GC patients resistant to standard therapy.
- Vaccination with a mixture of peptides derived from DEPDC1, URLC10, FoxM1, Kif20A, and VEGFR1.
- Assessment of safety, overall survival (OS), and immunological responses via ELISPOT assay, stratified by HLA-A24 positivity.
Main Results:
- The peptide vaccine was generally safe, with severe skin reactions in 4 patients being the main adverse event.
- No significant difference in overall survival (OS) was observed between HLA-A24-positive and HLA-A24-negative patients.
- In HLA-A24-positive patients, T-cell responses to antigen peptides, particularly DEPDC1, showed a trend towards better survival.
- Patients experiencing local skin reactions demonstrated significantly better OS.
Conclusions:
- Peptide vaccine therapy is safe and can induce specific T-cell responses in advanced gastric cancer patients.
- The study did not demonstrate a significant survival benefit for peptide vaccine monotherapy.
- Further clinical trials are required to confirm these preliminary findings and explore potential survival advantages.