Amin Hajitou
Imperial College London, UK
Keynote: J Neurol Neurophysiol
Current treatments for brain tumours have faced major challenges including lack of tumour selectivity and the bloodbrain
barrier (BBB). Development of a selective delivery system for brain tumours would play a major advance in
the treatment of these tumours. For instance, successful exploitation of numerous therapeutic agents depends, essentially
on the development of non-invasive nucleic acid delivery platforms. Indeed, gene therapy is promising in this disease
and brain tumours were the first to be treated by clinical gene therapy but success has been limited by the inefficiency of
vectors and by the BBB. We have used bacteriophage (phage), bacteria virus, to develop tumour targeted systemic vectors.
Phages have a historic safety profile as they have been administered to human over many years to treat infectious diseases.
Importantly, the filamentous M13 phage is able to traverse the BBB. However, phage has no strategies to deliver genes to
human cells. We reported a bacteriophage vector, as hybrid genome between two single-stranded DNA of human adenoassociated
virus (AAV) and filamentous M13 phage, termed AAV phage or AAVP, in which gene expression is under
the control of AAV genome. We and independent groups reported efficacy of selective intravenous cancer gene therapy,
with the RGD4C-AAVP displaying RGD4C ligand to target the tumour specific αvβ3 integrin receptor. To validate our
systemic delivery platform for brain tumours, we showed the ability of the phage vector administered intravenously to
home selectively to human glioblastoma (GBM), in preclinical models, through the BBB by binding the αvβ3 integrin,
subsequently delivering a recombinant rAAV genome that delivers a suicide gene therapy in tumour cells, angiogenic
endothelial cells and GBM-derived stem cells. Combination with a low dose of temozolomide (TMZ) enhanced gene
delivery/therapy by using a tumour specific promoter from an endogenous gene associated with GBM resistance to TMZ
chemotherapy. These findings provide evidence that bacteriophage is a promising delivery platform for use in targeted
treatment in neuro-oncology.
Recent Publications
1. Asavarut P and Hajitou A (2014) The phage revolution against antibiotic resistance. The Lancet Infectious
Diseases 14(8):657-778.
2. Kia A, Przystal JM, Nianiaris N, Mazarakis ND, Mintz PJ, Hajitou A (2012) Dual systemic tumor targeting
with ligand-directed phage and Grp78 promoter induces tumor regression. Molecular Cancer Therapeutics
11(12):2566-2577.
3. Hajitou A, Trepel M, Lilley C E, Soghomonyan S, Alauddin M M, Marini F C, 3rd, Restel B H, Ozawa M G,
Moya C A, Rangel R, Sun Y, Zaoui K, Schmidt M, von Kalle C, Weitzman MD, Gelovani J G, Pasqualini R and
Arap W (2006) A hybrid vector for ligand-directed tumor targeting and molecular imaging. Cell 125(2):385-98.
4. Frenkel D and Solomon B (2002) Filamentous phage as vector-mediated antibody delivery to the brain.
Proceedings of the National Academy of Sciences of the United States of America 99(8):5675-9.
5. Dubos R J, Straus J H and Pierce C (1943) the multiplication of bacteriophage in vivo and its protective effect
against an experimental infection with Shigella Dysnteriae. The Journal of Experimental Medicine 78(3):161-
168
Amin Hajitou completed his PhD at the University of Liege, Belgium, where he acquired extensive experience in delivery technologies for therapeutic nucleic acids. Then he did his Postdoctoral training in the world leading MD-Anderson Cancer Center in Texas-USA, where he gained expertise in bacteriophage (phage)-guided gene delivery and phage display technologies in vitro and in vivo. Importantly, he designed a novel hybrid phage vector for targeted nucleic acid transfer to cancer. The hybrid phage, published in Cell 2006, showed first success of systemic gene targeting to cancer in vivo. His team and independent groups reported efficacy of intravenous cancer gene therapy in rodents and pet dogs with naturally occurring cancers. In 2008, he established his research team, as a Lecturer, at Imperial College, then became Senior Lecturer in 2013 and Reader in 2016. His research team has become a leading authority in phage-guided delivery systems to cancer including brain tumours. His leadership in the field has resulted in various awards for his research and a Royal Decoration by his Majesty the King of Morocco, in 2015.
E-mail: a.hajitou@imperial.ac.uk
