Immunologic Evaluation of Personalized Peptide Vaccination for Patients with Advanced Malignant Glioma

• Published in: Clinical cancer research Vol. 11; no. 16; pp. 5900 - 5911
• Main Authors: YAJIMA, Naoki, YAMANAKA, Ryuya, YAMADA, Akira, SHIGEMORI, Minoru, ITOH, Kyogo, TANAKA, Ryuichi, MINE, Takashi, TSUCHIYA, Naoto, HOMMA, Jumpei, SANO, Masakazu, KURAMOTO, Terukazu, OBATA, Yayoi, KOMATSU, Nobukazu, ARIMA, Yoshimi
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-08-2005
• Subjects: Adult; Aged; Antigens, Neoplasm - genetics; Antineoplastic agents; Biological and medical sciences; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - immunology; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Female; Gene Expression Regulation, Neoplastic - immunology; Glioma - drug therapy; Glioma - genetics; Glioma - immunology; HLA-A Antigens - immunology; HLA-A2 Antigen - immunology; HLA-A24 Antigen; Humans; Immunoglobulin G - blood; Immunoglobulin G - cerebrospinal fluid; immunotherapy; Leukocytes, Mononuclear - immunology; Male; malignant glioma; Medical sciences; Middle Aged; Neurology; Peptides - immunology; Peptides - therapeutic use; personalized peptide vaccination; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Survival Analysis; T-Lymphocytes, Cytotoxic - immunology; Treatment Outcome; Tumors of the nervous system. Phacomatoses; Human; Prevention; Evaluation; Malignant glioma; Nervous system diseases; Peptides; Vaccination; Central nervous system disease; Advanced stage; Malignant tumor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-0559

Purpose: 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.
Experimental Design: 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.