Brain glioma is one of the cancer types with worst prognosis, and LMO2 has been reported to play oncogenic functions in brain gliomas. Herein, analysis of datasets from The Cancer Genome Atlas (TCGA) indicated that higher LMO2 level in patient samples indicated worse prognosis in lower grade gliomas (LGG) but not glioblastoma multiforme (GBM). Further, in tumor tissues consisting of a variety of cell types, LMO2 level indicated intratumoral endothelium and pattern recognition receptor (PRR) response in both LGGs and GBMs, and additionally indicated cytotoxic T-lymphocyte, M2 macrophage infiltration and fibroblast specifically in LGGs. Moreover, only in LGGs these aspects were significantly associated with patient survival, in either risky or protective manner, and these dissected associations can give a better prediction on patient prognosis than LMO2 alone. This study not only provided more detailed understandings of LMO2 functional representatives in brain gliomas but also demonstrated that dealing with certain gene (LMO2 in this study) in transcriptome data with the Weighted Gene Co-Expression Network Analysis (WGCNA) method was a robust strategy for dissecting exact and reasonable gene functions/associations in a complicated tumor environment.

Despite a major improvement in the treatment of advanced kidney cancer by the recent introduction of targeted agents such as multi-kinase inhibitors, long-term benefits are still limited and a significant unmet medical need remains for this disease. Cancer immunotherapy has shown its potential by the induction of long-lasting responses in a small subset of patients, however, the unspecific immune interventions with (high dose) cytokines used so far are associated with significant side effects. Specific cancer immunotherapy may circumvent these problems by attacking tumor cells while sparing normal tissue with the use of multi-peptide vaccination being one of the most promising strategies. We here summarize the clinical and translational data from phase I and II trials investigating IMA901. Significant associations of clinical benefit with detectable T cell responses against the IMA901 peptides and encouraging survival data in treated patients has prompted the start of a randomized, controlled phase III trial in 1st line advanced RCC with survival results expected toward the end of 2015. Potential combination strategies with the recently discovered so-called checkpoint inhibitors are also discussed.

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4(+) T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.

The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients.

Dendritic cell (DC) immunotherapy is emerging as a potential addition to the standard of care in the treatment of glioblastoma multiforme (GBM). In the last decade or so various research groups have conducted phase I and II trials of DC-immunotherapy on patients with newly diagnosed (ND) and recurrent GBM and other high-grade gliomas in an attempt to improve the poor prognosis. Results show an increase in overall survival (OS), while vaccination-related side effects are invariably mild. Northwest Biotherapeutics, Inc., Bethesda, Maryland, U.S.A. (NWBT) developed the DCVax®-L vaccine as an adjunct to the treatment of GBM. It is currently under evaluation in a phase III trial in patients with ND-GBM, which is the only ongoing trial of its kind. In this review current data and perspectives of this product are examined.