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Cancer Immunol Immunother. 2016 Nov;65(11):1339-1352. Epub 2016 Aug 30.

Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma.

Author information

1
Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. robert.fenstermaker@roswellpark.org.
2
Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. robert.fenstermaker@roswellpark.org.
3
Center for Immunotherapy, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. robert.fenstermaker@roswellpark.org.
4
Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
5
Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
6
Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
7
Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
8
Center for Immunotherapy, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
9
Department of Neuro-Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
10
Department of Diagnostic Imaging, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
11
Department of Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.

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.

KEYWORDS:

Apoptosis; Glioma; Immunotherapy; Peptide; Survivin; Vaccine

PMID:
27576783
PMCID:
PMC5069322
DOI:
10.1007/s00262-016-1890-x
[Indexed for MEDLINE]
Free PMC Article

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