title: Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma.
abstract: Survivin is an anti-apoptotic protein that is highly expressed in many cancers, including malignant gliomas. Preclinical studies established that the conjugated survivin peptide mimic SurVaxM (SVN53-67/M57-KLH) could stimulate an anti-tumor immune response against murine glioma in vivo, as well as human glioma cells ex vivo. The current clinical study was conducted to test safety, immunogenicity and clinical effects of the vaccine. Recurrent malignant glioma patients whose tumors were survivin-positive, and who had either HLA-A*02 or HLA-A*03 MHC class I allele-positivity, were given subcutaneous injections of SurVaxM (500 μg) in Montanide ISA 51 with sargramostim (100 μg) at 2-week intervals. SurVaxM was well tolerated with mostly grade one adverse events (AE) and no serious adverse events (SAE) attributable to the study drug. Six patients experienced local injection site reactions; three patients reported fatigue (grades 1 and 2), and 2 patients experienced myalgia (grade 1). Six of eight immunologically evaluable patients developed both cellular and humoral immune responses to vaccine. The vaccine also stimulated HLA-A*02, HLA-A*03 and HLA-A*24 restricted T cell responses. Three patients maintained a partial clinical response or stable disease for more than 6 months. Median progression-free survival was 17.6 weeks, and median overall survival was 86.6 weeks from study entry with seven of nine patients surviving more than 12 months.
authors: Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. robert.fenstermaker@roswellpark.org.|Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. robert.fenstermaker@roswellpark.org.|Center for Immunotherapy, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. robert.fenstermaker@roswellpark.org.
authors: Robert A
authors: RA
authors: Fenstermaker
authors: Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.|Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Michael J
authors: 0000-0002-3373-9421
authors: MJ
authors: Ciesielski
authors: Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Jingxin
authors: J
authors: Qiu
authors: Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.|Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Nuo
authors: N
authors: Yang
authors: Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Cheryl L
authors: CL
authors: Frank
authors: Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.|Center for Immunotherapy, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Kelvin P
authors: KP
authors: Lee
authors: Department of Neuro-Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Laszlo R
authors: LR
authors: Mechtler
authors: Department of Diagnostic Imaging, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Ahmed
authors: A
authors: Belal
authors: Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
authors: Manmeet S
authors: MS
authors: Ahluwalia
authors: Department of Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors: Alan D
authors: AD
authors: Hutson
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D015789:HLA-A2 Antigen / Q000378:metabolism; D015791:HLA-A3 Antigen / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D016233:Immunotherapy, Active / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D016019:Survival Analysis; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; C524866:HLA-A*02 antigen; C487960:HLA-A*03 antigen; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D000077022:Survivin; D022223:Vaccines, Subunit; D007371:Interferon-gamma
keywords: Apoptosis; Glioma; Immunotherapy; Peptide; Survivin; Vaccine