Vaccination with predesignated or evidence-based peptides for patients with recurrent gynecologic cancers.
Two different trials of peptide vaccination were conducted for patients with recurrent gynecologic cancers. In the first regimen, four HLA-A24+ patients (two with cervical cancer and two with ovarian cancer) were vaccinated with peptides that were predesignated before vaccination. Three patients exhibited with a grade 1 adverse effect, and no clinical response was observed in any patients. In the second regimen, six HLA-A24+ and four HLA-A2+ patients (five with cervical cancer, one with endometrial cancer, one with uterine sarcoma, and three with ovarian cancer) were vaccinated with peptides (maximum four) to which preexisting cytotoxic T lymphocyte precursors in the periphery were confirmed before vaccination. With this regimen, grade 1 adverse effects were observed in eight patients, a grade 2 adverse effect in one patient, and a grade 3 adverse effect (ie, rectal bleeding) in one patient. However, this regimen was able to enhance peptide-specific cytotoxic T lymphocytes in seven of ten patients, and three of five cervical cancer patients showed objective tumor regression. Analysis of immunoglobulin G -reactive to administered peptides suggested that the induction of peptide-specific immunoglobulin G was correlated with clinical responses. Overall, these results suggest that peptide vaccination of patients showing evidence of preexisting peptide-specific cytotoxic T lymphocyte precursors could be superior to vaccination with predesignated peptides, and that the evidence-based regimen is applicable for clinical trials in treatment of patients with recurrent gynecologic cancers.
Tsuda
Naotake
N
Departments of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Mochizuki
Kazuo
K
Harada
Mamoru
M
Sukehiro
Aki
A
Kawano
Koichiro
K
Yamada
Akira
A
Ushijima
Kimio
K
Sugiyama
Toru
T
Nishida
Takashi
T
Yamana
Hideaki
H
Itoh
Kyogo
K
Kamura
Toshiharu
T
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002296:Carcinosarcoma / Q000628:therapy; D016889:Endometrial Neoplasms / Q000628:therapy; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000628:therapy; D012882:Skin Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000628:therapy; D014611:Vaccination; D022223:Vaccines, Subunit / Q000493:pharmacokinetics / Q000627:therapeutic use*
D019496:Cancer Vaccines; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D022223:Vaccines, Subunit