Immunotherapeutic benefit of α-interferon (IFNα) in survivin2B-derived peptide vaccination for advanced pancreatic cancer patients.
Survivin, a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain, is highly expressed in cancerous tissues but not in normal counterparts. Our group identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), that is recognized by CD8 + CTLs and functions as an immunogenic molecule in patients with cancers of various histological origins such as colon, breast, lung, oral, and urogenital malignancies. Subsequent clinical trials with this epitope peptide alone resulted in clinical and immunological responses. However, these were not strong enough for routine clinical use as a therapeutic cancer vaccine, and our previous study of colon cancer patients indicated that treatment with a vaccination protocol of survivin-2B80-88 plus incomplete Freund's adjuvant (IFA) and α-interferon (IFNα) conferred overt clinical improvement and enhanced the immunological responses of patients. In the current study, we further investigated whether this vaccination protocol could efficiently provide not only improved immune responses but also better clinical outcomes for advanced pancreatic cancers. Tetramer and enzyme-linked immunosorbent spot analysis data indicated that more than 50% of the patients had positive clinical and immunological responses. In contrast, assessment of treatment with IFNα only to another group of cancer patients resulted in no obvious increase in the frequency of survivin-2B80-88 peptide-specific CTLs. Taken together, our data clearly indicate that a vaccination protocol of survivin-2B80-88 plus IFA and IFNα is very effective and useful in immunotherapy for this type of poor-prognosis neoplasm. This trial was registered with the UMIN Clinical Trials Registry, no. UMIN000000905.
Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hidekazu
H
Kameshima
Tetsuhiro
T
Tsuruma
Goro
G
Kutomi
Hiroaki
H
Shima
Yuji
Y
Iwayama
Yasutoshi
Y
Kimura
Masahumi
M
Imamura
Toshihiko
T
Torigoe
Akari
A
Takahashi
Yoshihiko
Y
Hirohashi
Yasuaki
Y
Tamura
Tomohide
T
Tsukahara
Takayuki
T
Kanaseki
Noriyuki
N
Sato
Koichi
K
Hirata
D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy; D005260:Female; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000628:therapy*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D059871:HLA-A24 Antigen; D051034:Inhibitor of Apoptosis Proteins; D016898:Interferon-alpha; D000077022:Survivin; D022223:Vaccines, Subunit