Oncotarget

Research Papers:

Glioblastoma-specific anti-TUFM nanobody for in-vitro immunoimaging and cancer stem cell targeting

Neja Samec, Ivana Jovcevska, Jure Stojan, Alja Zottel, Mirjana Liovic, Michael P. Myers, Serge Muyldermans, Jernej Šribar, Igor Križaj and Radovan Komel _

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Oncotarget. 2018; 9:17282-17299. https://doi.org/10.18632/oncotarget.24629

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Abstract

Neja Samec1, Ivana Jovcevska1, Jure Stojan1, Alja Zottel1, Mirjana Liovic1, Michael P. Myers2, Serge Muyldermans3, Jernej Šribar4, Igor Križaj4 and Radovan Komel1

1Medical Centre for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

2International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

3Cellular and Molecular Immunology, Bioengineering Sciences Department, Vrije Universiteit Brussel, Brussels, Belgium

4Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia

Correspondence to:

Radovan Komel, email: [email protected]

Neja Samec, email: [email protected]

Keywords: glioblastoma multiforme; biomarkers; nanobodies; cytotoxicity; TUFM

Received: October 20, 2017     Accepted: February 24, 2018     Published: April 03, 2018

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and lethal form of brain tumor. The prognosis for patients remains poor, despite the combination of new preoperative and intraoperative neuroimaging, radical surgery, and recent advances in radiotherapy and chemotherapy. To improve GBM therapy and patient outcome, sustained drug delivery to glioma cells is needed, while minimizing toxicity to adjacent neurons and glia cells. This might be achieved through an anti-proteomic approach based on nanobodies, the single-domain antigen-binding fragments of heavy-chain antibodies of the camelid adaptive immune system. We report here on the validation and quantification of a nanobody raised against mitochondrial translation elongation factor (TUFM). Differential expression of TUFM was examined in different GBM cell lines and GBM tissue at the protein and mRNA levels, as compared to their expression in neural stem cells and normal brain tissue. We further used in-silico modelling and immunocytochemistry to define the specificity of anti-TUFM nanobody (Nb206) towards GBM stem cells, as compared to GBM cell lines (U251MG and U87MG cells). Due to its specificity and pronounced inhibitory effect on GBM stem cell growth, we propose the use of this anti-TUFM nanobody for GBM in vitro immunoimaging and potentially also cancer stem cell targeting.


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