Phase I vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma

Journal of Translational Medicine

Toshihiko Yamashita¹  Noriyuki Sato²  Shin-ichiro Tatezaki⁴  Takeshi Ishii⁴  Hiroaki Hiraga⁵  Toshihiko Torigoe²  Hiroko Asanuma²  Kumiko Shimozawa³  Hideyuki Ikeda²  Hiroeki Sahara⁶  Sigeharu Kimura²  Tomohide Tsukahara²  Satoshi Nagoya¹  Yuriko Sato¹  Kazunori Ida²  Takuro Wada¹  Satoshi Kawaguchi¹ 

[1] Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan;Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan;Cancer Vaccine Laboratory, Innovation Plaza Hokkaido, Japan Science and Technology Corporation, Sapporo, Japan;Division of Orthopaedic Surgery, Chiba Cancer Center Hospital, Chiba, Japan;Division of Orthopedics, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan;Marine Biomedical Institute, Sapporo Medical University School of Medicine, Rishirifuji, Japan

关键词: Phase I trial;    vaccination;    antigenic peptide;    SYT-SSX;    Synovial sarcoma;   

Others  :  1208515
DOI  :  10.1186/1479-5876-3-1

 received in 2004-12-06, accepted in 2005-01-12,  发布年份 2005

【 摘 要 】

Background

Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma.

Methods

A 9-mer peptide (SYT-SSX B: GYDQIMPKK) spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i) who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive), (ii) HLA-A*2402 positive, (iii) between 20 and 70 years old, (iv) ECOG performance status between 0 and 3, and (v) who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg) were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction.

Results

A total of 16 vaccinations were carried out in six patients. The results were (i) no serious adverse effects or DTH reactions, (ii) suppression of tumor progression in one patient, (iii) increases in the frequency of peptide-specific CTLs in three patients and a decrease in one patient, and (iv) successful induction of peptide-specific CTLs from four patients.

Conclusions

Our findings indicate the safety of the SYT-SSX junction peptide in the use of vaccination and also give support to the property of the peptide to evoke in vivo immunological responses. Modification of both the peptide itself and the related protocol is required to further improve the therapeutic efficacy.

【 授权许可】

   
2005 Kawaguchi et al; licensee BioMed Central Ltd.

【 图 表 】

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