Measles Virotherapy
Measles virus (MV) is one of the most contagious human pathogens. It is transmitted by aerosols, infecting a new host via the upper respiratory tract. Eventually, infection can spread to many organs of the body. The host cell receptors for MV are well defined: CD46, a member of the human complement regulatory proteins and a ubiquitous cellular receptor found on all nucleated cells, and CD150 or SLAM (signalling lymphocyte activation molecule), a membrane glycoprotein present on activated B cells, T cells and monocytes. It is generally believed that laboratory and vaccine strains of MV use both CD150 and CD46 as their cellular receptors, but wild-type MV strains mainly use CD150.
Oncolytic viruses have been selected or engineered to replicate in tumour cells. Approaches towards targeting cancer cells frequently exploit antigens that are unique to or are over expressed on the surface of tumour cells. As cell surface recognition and virus entry is the key first step for specific targeting, engineering oncolytic viruses in order to recognize exclusively the tumour cell-surface is important. Therefore, retargeting of oncolytic viruses a promising approach to exploit the potential of virotherapy.
In a recently published paper (Genetically engineered attenuated measles virus specifically infects and kills primary multiple myeloma cells. J Gen Virol. 2009 90: 693-701), researchers describe use of a mouse monoclonal antibody Wue-1, which is specific for B cells and their malignant counterparts, to retarget a CD46- and CD150-blinded recombinant MV towards Wue-1+ cells. This engineered virus with altered receptors specifically and efficiently infected primary multiple myeloma cells and induced apoptosis.
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Although virotherapy of hard-to-treat tumours with engineered viruses is a tantalizing prospect, this approach is still limited to laboratory studies at present. In order to develop a practical oncolytic treatments, successful tests in vitro using susceptible cells must lead to evaluation of the efficacy of tumour reduction in vivo in animal models with objective measurable parameters of safety and efficacy. Only then will we be ready to begin consideration of human trials of these potent new weapons in the fight against cancer.
Related:
- How Measles Virus Infects Cells
- Measles vaccination and SSPE
- Measles and Mumps in the USA
- Measles virus: cellular receptors, tropism and pathogenesis. J Gen Virol. 2006 87: 2767-2779
Tags: Biology, Biotechnology, Health, Medicine, Microbiology, Podcast, Science, Virology
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