Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*2402
Open Access
- 16 September 2010
- journal article
- Published by Springer Science and Business Media LLC in Journal of Translational Medicine
- Vol. 8 (1), 84
- https://doi.org/10.1186/1479-5876-8-84
Abstract
Background: The tumor associated antigen (TAA) gp100 was one of the first identified and has been used in clinical trials to treat melanoma patients. However, the gp100 epitope peptide restricted to HLA-A*2402 has not been extensively examined clinically due to the ethnic variations. Since it is the most common HLA Class I allele in the Japanese population, we performed a phase I clinical trial of cancer vaccination using the HLA-A*2402 gp100 peptide to treat patients with metastatic melanoma.Methods: The phase I clinical protocol to test a HLA-A*2402 gp100 peptide-based cancer vaccine was designed to evaluate safety as the primary endpoint and was approved by The University of Tokyo Institutional Review Board. Information related to the immunologic and antitumor responses were also collected as secondary endpoints. Patients that were HLA-A*2402 positive with stage IV melanoma were enrolled according to the criteria set by the protocol and immunized with a vaccine consisting of epitope peptide (VYFFLPDHL, gp100-in4) emulsified with incomplete Freund's adjuvant (IFA) for the total of 4 times with two week intervals. Prior to each vaccination, peripheral blood mononuclear cells (PBMCs) were separated from the blood and stored at -80°C. The stored PBMCs were thawed and examined for the frequency of the peptide specific T lymphocytes by IFN-γ- ELISPOT and MHC-Dextramer assays.Results: No related adverse events greater than grade I were observed in the six patients enrolled in this study. No clinical responses were observed in the enrolled patients although vitiligo was observed after the vaccination in two patients. Promotion of peptide specific immune responses was observed in four patients with ELISPOT assay. Furthermore, a significant increase of CD8+gp100-in4+CTLs was observed in all patients using the MHC-Dextramer assay. Cytotoxic T lymphocytes (CTLs) clones specific to gp100-in4 were successfully established from the PBMC of some patients and these CTL clones were capable of lysing the melanoma cell line, 888 mel, which endogenously expresses HLA-restricted gp100-in4.Conclusion: Our results suggest this HLA-restricted gp100-in4 peptide vaccination protocol was well-tolerated and can induce antigen-specific T-cell responses in multiple patients. Although no objective anti-tumor effects were observed, the effectiveness of this approach can be enhanced with the appropriate modifications.Keywords
This publication has 49 references indexed in Scilit:
- Treatment of Metastatic Melanoma Using Interleukin-2 Alone or in Conjunction with VaccinesClinical Cancer Research, 2008
- Vaccines for tumour preventionNature Reviews Cancer, 2006
- Innate Immunity Gone Awry: Linking Microbial Infections to Chronic Inflammation and CancerCell, 2006
- Processing and presentation of tumor antigens and vaccination strategiesCurrent Opinion in Immunology, 2006
- Phase 2 Study of the g209-2M Melanoma Peptide Vaccine and Low-Dose Interleukin-2 in Advanced MelanomaJournal of Immunotherapy, 2006
- Rationale for Antiangiogenic Cancer Therapy with Vaccination Using Epitope Peptides Derived from Human Vascular Endothelial Growth Factor Receptor 2Cancer Research, 2005
- Smoldering and polarized inflammation in the initiation and promotion of malignant diseaseCancer Cell, 2005
- Initiation and regulation of CD8+T cells recognizing melanocytic antigens in the epidermis: Implications for the pathophysiology of vitiligoEuropean Journal of Cell Biology, 2004
- DNA typing of the HLA‐A gene: population study and identification of four new alleles in JapaneseTissue Antigens, 1996
- A Gene Encoding an Antigen Recognized by Cytolytic T Lymphocytes on a Human MelanomaScience, 1991