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An HLA-A3-binding prostate acid phosphatase-derived peptide can induce CTLs restricted to HLA-A2 and -A24 alleles
Yasunobu Terasaki1, Shigeki Shichijo, Yamei Niu
1Department of Immunology and Immunotherapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Abstract:
We previously reported peptide vaccine candidates for HLA-A3 supertype (-A3, -A11, -A31, -A33)-positive cancer patients. In the present study, we examined whether those peptides can also induce cytotoxic T lymphocyte (CTL) activity restricted to HLA-A2, HLA-A24, and HLA-A26 alleles. Fourteen peptides were screened for their binding activity to HLA-A*0201, -A*0206, -A*0207, -A*2402, and -A*2601 molecules and then tested for their ability to induce CTL activity in peripheral blood mononuclear cells (PBMCs) from prostate cancer patients. Among these peptides, one from the prostate acid phosphatase protein exhibited binding activity to HLA-A*0201, -A*0206, and -A*2402 molecules. In addition, PBMCs stimulated with this peptide showed that HLA-A2 or HLA-A24 restricted CTL activity. Their cytotoxicity toward cancer cells was ascribed to peptide-specific and CD8+ T cells. These results suggest that this peptide could be widely applicable as a peptide vaccine for HLA-A3 supertype-, HLA-A2-, and -A24-positive cancer patients.
Insights
A novel peptide vaccine candidate shows potential for broad cancer patient application. This prostate cancer-derived peptide effectively induces cytotoxic T lymphocyte (CTL) activity in patients with HLA-A2 or HLA-A24 alleles, expanding vaccine eligibility.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Previous research identified peptide vaccine candidates for HLA-A3 supertype-positive cancer patients.
- The current study investigates the efficacy of these peptides in inducing cytotoxic T lymphocyte (CTL) activity restricted to HLA-A2, HLA-A24, and HLA-A26 alleles.
Purpose of the Study:
- To screen peptide vaccine candidates for binding affinity to specific HLA alleles (HLA-A*0201, -A*0206, -A*0207, -A*2402, -A*2601).
- To evaluate the ability of these peptides to induce CTL activity in peripheral blood mononuclear cells (PBMCs) from prostate cancer patients.
- To determine the potential of a specific peptide for broader application in cancer immunotherapy.
Main Methods:
- Screening of fourteen peptides for binding activity to five HLA-A alleles.
- Testing peptide-induced CTL activity in PBMCs from prostate cancer patients.
- Characterization of CTL activity, including T cell subset (CD8+) and specificity.
Main Results:
- One prostate acid phosphatase-derived peptide demonstrated binding to HLA-A*0201, -A*0206, and -A*2402 molecules.
- This peptide successfully induced HLA-A2 and HLA-A24 restricted CTL activity in patient PBMCs.
- The observed cytotoxicity was mediated by peptide-specific, CD8+ T cells.
Conclusions:
- A peptide vaccine candidate targeting prostate acid phosphatase shows broad applicability.
- This peptide can induce CTL activity in cancer patients positive for HLA-A3 supertype, HLA-A2, and HLA-A24 alleles.
- The findings support the development of this peptide for a wider range of cancer patients.
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