Replicating Attenuated Measles Virus Can Be Engineered to Enter Cells Through the CD20 Antigen
Ultima Vez Modificado: 10 de diciembre de 2002
Presenter: Adele Fielding
Presenter's Affiliation: Mayo Clinic
Type of Session: Scientific
- In laboratory models of Non-Hodgkin's Lymphoma (NHL), attenuated measles virus (MV) has been found to have therapeutic potential as a replicating, oncolytic virus.
- There are case reports of lymphoma regression after measles virus infection in people.
- The measles virus is a negative strand RNA virus with lymphoid cell tropism.
- CD20 is a lympocyte cell surface antigen, an important target in NHL therapy.
- The study describes the development of a CD20 seeking MV and its subsequent in-vivo and in-vitro testing.
- The H envelope glycoprotein of MV was replaced by an H-scFVanti CD20 fusion protein with specific CD20 targeted binding.
- The replication of this virus was then tested on CD20 positive and negative cell lines in vitro.
- CD20 positive and negative tumor grafts were grown in SCID mice which were then treated with the live attenuated virus.
- Western blot analysis confirmed the presence of anti-CD20 fusion protein in live replicating virus.
- MV expressing anti-CD20 replicated well in non-permissive CD20 positive CHO cells. Wild-type virus replicated poorly in these cells.
- Anti-CD20 expressing MV grew poorly in non-CD20 expressing CHO cells.
- Proteolytic cleavage of the anti-CD20 protein from MV obliterated their ability to replicate in CD20 positive CHO cells.
- Anti-CD20 expressing MV was much better at suppressing growth of CD20 positive tumor xenografts than wild-type MV.
- This is the first data to show the entry and replication of an oncolytic virus specific for a clinically relevent cellular target protein.
- In-vivo tumor regression is seen when CD20 positive tumor is treated with modified MV.
- The next goal is to further engineer the virus to eliminate binding to CD46 and SLAM, its natural targets.
- The CD20 antigen is important for the treatment of NHL. This study illustrates one other mechanism by which the CD20 antigen can help target cytotoxic mechanisms to tumor cells. Further laboratory study to eliminate unwanted binding to the native MV target epitopes and to ensure safety is warranted prior to considering human testing.
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