Open AccessPhase I clinical trial of survivin‐derived peptide vaccine therapy for patients with advanced or recurrent oral cancer
Author(s) -
Miyazaki Akihiro,
Kobayashi Junichi,
Torigoe Toshihiko,
Hirohashi Yoshihiko,
Yamamoto Takashi,
Yamaguchi Akira,
Asanuma Hiroko,
Takahashi Akari,
Michifuri Yoshitaka,
Nakamori Kenji,
Nagai Itaru,
Sato Noriyuki,
Hiratsuka Hiroyoshi
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01789.x
Subject(s) - medicine , survivin , peptide vaccine , cancer , immunology , clinical trial , vaccination , antigen , adverse effect , cancer vaccine , cd8 , peripheral blood mononuclear cell , tumor antigen , immunotherapy , ctl* , adjuvant , oncology , epitope , in vitro , biology , biochemistry
Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. Previously we have identified a human leukocyte antigen (HLA)‐A24‐restricted antigenic peptide, survivin‐2B80‐88 (AYACNTSTL), recognized by CD8 + cytotoxic T lymphocytes (CTL). Survivin‐2B80‐88‐specific CTL were induced efficiently from peripheral blood mononuclear cells (PBMC) of oral cancer patients after stimulation with the peptide in vitro . We conducted a phase I clinical study to evaluate the safety and the efficacy of survivin‐2B80‐88 peptide vaccination in HLA‐A24‐positive patients with advanced or recurrent oral cancer. The vaccines were given subcutaneously or intratumorally six times at 14‐day intervals. Eleven patients were enrolled and 10 patients completed the vaccination protocol. No adverse events were observed in any patients. In two patients, the levels of serum squamous cell carcinoma (SCC) antigen decreased transiently during the period of vaccination. Tumor regression that was compatible with a partial response (PR) was noted in one patient. The remaining nine patients experienced progressive disease (PD). Immunologically, an increase of the peptide‐specific CTL frequency was detected in six of the eight patients evaluated by HLA‐A24/peptide tetramer analysis. The present clinical trial revealed that survivin‐2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. However, subsequent clinical trials in combination with various adjuvant drugs will be required to improve the immunological and therapeutic efficacy. This trial was registered with University Hospital Medical Information Network (UMIN) number UMIN976. ( Cancer Sci 2011; 102: 324–329)