Immunologic evaluation of personalized peptide vaccination for patients with advanced malignant glioma.
OBJECTIVE
The primary goal of this phase I study was to assess the safety and immunologic responses of personalized peptide vaccination for patients with advanced malignant glioma.


METHODS
Twenty-five patients with advanced malignant glioma (8 grade 3 and 17 grade 4 gliomas) were evaluated in a phase I clinical study of a personalized peptide vaccination. For personalized peptide vaccination, prevaccination peripheral blood mononuclear cells and plasma were provided to examine cellular and humoral responses to 25 or 23 peptides in HLA-A24+ or HLA-A2+ patients, respectively; then, only the reactive peptides (maximum of four) were used for in vivo administration.


RESULTS
The protocols were well tolerated with local redness and swelling at the injection site in most cases. Twenty-one patients received more than six vaccinations and were evaluated for both immunologic and clinical responses. Increases in cellular or humoral responses specific to at least one of the vaccinated peptides were observed in the postvaccination (sixth) samples from 14 or 11 of 21 patients, respectively. More importantly, significant levels of peptide-specific IgG were detected in the postvaccination tumor cavity or spinal fluid of all of the tested patients who showed favorable clinical responses. Clinical responses were 5 partial responses, 8 cases of stable disease, and 8 cases of progressive disease. The median overall survival for patients with recurrent glioblastoma multiforme in this study (n = 17) was 622 days.


CONCLUSIONS
Personalized peptide vaccinations were recommended for the further clinical study to malignant glioma patients.
Yajima
Naoki
N
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.
Yamanaka
Ryuya
R
Mine
Takashi
T
Tsuchiya
Naoto
N
Homma
Jumpei
J
Sano
Masakazu
M
Kuramoto
Terukazu
T
Obata
Yayoi
Y
Komatsu
Nobukazu
N
Arima
Yoshimi
Y
Yamada
Akira
A
Shigemori
Minoru
M
Itoh
Kyogo
K
Tanaka
Ryuichi
R
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D010455:Peptides; D012333:RNA, Messenger