Tumor Vaccines for Malignant Gliomas

Srinivasan, Visish M.; Ferguson, Sherise D.; Lee, Sung-Ho; Weathers, Shiao Pei; Kerrigan, Brittany C. Parker; Heimberger, Amy B.

doi:10.1007/s13311-017-0522-2

Cited by 42 publications

(44 citation statements)

References 115 publications

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“…Proteomics 18, 1255Proteomics 18, -1268. ent cancers, including GBM, has drawn significant attention (3,4), reviewed in (5)(6)(7)(8)(9)(10)(11)(12)(13). Much of the recent excitement about cancer immunotherapy stems from the success in treating patients with immune checkpoint modulators, which induce anti-cancer T cell immune reactions that can break tolerance and bring about complete responses in increasingly larger percentages of patients (14,15).…”

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confidence: 99%

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Shraibman¹,

Barnea²,

Kadosh³

et al. 2018

Molecular & Cellular Proteomics

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Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples. Tumor samples were fresh-frozen immediately after surgery and the plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the individual patients, whereas low correlations were observed between these HLA peptidomes and the tumors' proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.

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confidence: 99%

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Shraibman¹,

Barnea²,

Kadosh³

et al. 2018

Molecular & Cellular Proteomics

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“…3,4 As has recently been the case with cancer, in general, there has been much interest in the use of immunotherapy against glioblastoma. Preclinical demonstration of the efficacy of vaccination has led to several randomized phase 2 and phase 3 clinical studies, including with peptides, 5 dendritic cells, 6 and heat shock proteins derived from patient tumor specimens. 7,8 While much important work continues, initial results from several high-profile trials have been negative.…”

Section: Introductionmentioning

confidence: 99%

Triple combination immunotherapy with GVAX, anti-PD-1 monoclonal antibody, and agonist anti-OX40 monoclonal antibody is highly effective against murine intracranial glioma

et al. 2019

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Single-agent immunotherapy, including with immune checkpoint inhibition with anti-PD-1 antibody, has not extended survival in patients with malignant glioma. However, PD-1 inhibition may still play a role in combination immunotherapy with multiple agents. In this study, we evaluated anti-PD-1 antibody treatment in combination with multiple approaches, including vaccination and agonist anti-OX40 immunotherapy, as well as triple combination immunotherapy with each of the above agents in a murine glioma model. Treatments were delivered on days 3,6, and 9 after intracranial implantation of glioma cells in the right frontal lobes of the mice. Vaccination consisted of subcutaneous implantation of irradiated GL261 cells engineered to express GM-CSF. We harvested splenocytes and brain tissue 18 days after glioma implantation and analyzed them by ELISPOT and flow cytometry, respectively. Treated mice surviving for 120 days were challenged with implantation of large numbers of GL261 cells and either followed for survival or sacrificed for study of the memory response. Survival was assessed by the Kaplan-Meier method and the log-rank test. Means were compared by the 2-tailed student's t-test. We report that combining anti-PD-1 immunotherapy with either vaccination or agonist anti-OX40 immunotherapy improves survival in GL261-bearing mice compared with any of the above as monotherapy. Triple combination immunotherapy with vaccination, anti-PD-1 antibody, and agonist anti-OX 40 antibody results in long-term survival in all mice. Triple combination immunotherapy resulted in an elevated CD4+/CD8 + T lymphocyte ratio amongst tumor-infiltrating lymphocytes as well as a diminished fraction of regulatory T lymphocytes, likely reflective of a more vigorous Th1 antitumor response. ARTICLE HISTORY

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“…More precisely, vaccines aim at inducing tumor-specific immune responses, mainly based on CD8 + cytotoxic T lymphocytes (CTL), which are specific to tumor antigens [10]. According to the strategy used to present the antigens to the immune system, cancer vaccines can be divided mainly in two groups, cell-free or cell-based vaccines [11].…”

Section: The Spectrum Of Vaccine Strategies In Glioblastomamentioning

confidence: 99%

Impact of Immunotherapy in the Treatment of Glioblastoma

Silva¹,

Miranda²,

Sousa³

et al. 2018

Biopharmaceuticals

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Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. Despite the efforts developed in the respective treatment, consisting of maximal surgical resection followed by adjuvant radiotherapy and chemotherapy, the prognosis remains very poor. This may be partly related to the resistance of GBM cells and their infiltrative and invasive nature into the surrounding brain tissue. Therefore, newer and challenging alternative approaches for the treatment have emerged, including immunotherapy. This anticancer therapy, based on the stimulation of the host's immune system, has been currently investigated and several advances in the clinical trial stage have already been reached. Immunotherapeutic strategies comprise a set of modalities, including vaccines (cell-free and cell-based), chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, monoclonal antibodies (mAbs), and oncolytic viruses (OVs). In this chapter, we will review the principal concepts and the recent progress in immunotherapy for GBM.

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Tumor Vaccines for Malignant Gliomas

Cited by 42 publications

References 115 publications

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

Triple combination immunotherapy with GVAX, anti-PD-1 monoclonal antibody, and agonist anti-OX40 monoclonal antibody is highly effective against murine intracranial glioma

Impact of Immunotherapy in the Treatment of Glioblastoma

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