SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group.
In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.
Departments of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan. kawaguch@sapmed.ac.jp
Satoshi
S
Kawaguchi
Tomohide
T
Tsukahara
Kazunori
K
Ida
Shigeharu
S
Kimura
Masaki
M
Murase
Masanobu
M
Kano
Makoto
M
Emori
Satoshi
S
Nagoya
Mitsunori
M
Kaya
Toshihiko
T
Torigoe
Emiri
E
Ueda
Akari
A
Takahashi
Takeshi
T
Ishii
Shin-ichiro
S
Tatezaki
Junya
J
Toguchida
Hiroyuki
H
Tsuchiya
Toshihisa
T
Osanai
Takashi
T
Sugita
Hideshi
H
Sugiura
Makoto
M
Ieguchi
Koichiro
K
Ihara
Ken-ichiro
K
Hamada
Hiroshi
H
Kakizaki
Takeshi
T
Morii
Taketoshi
T
Yasuda
Taisuke
T
Tanizawa
Akira
A
Ogose
Hiroo
H
Yabe
Toshihiko
T
Yamashita
Noriyuki
N
Sato
Takuro
T
Wada
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000276:immunology*; D013584:Sarcoma, Synovial / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D019496:Cancer Vaccines; D015234:HLA-A Antigens; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; D022223:Vaccines, Subunit