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Johanna Kaufmann, PhD student
Helmholtz University Group Oncolytic Adenoviruses, DKFZ (German Cancer Research Center)
and Department of Dermatology, Heidelberg University Hospital
Im Neuenheimer Feld 242
+49 (0)6221 42-4451
Targeted Cell Entry
Virotherapy with oncolytic adenoviruses or measles viruses is a promising approach to combat cancers such as malignant melanoma. A prerequisite for this therapeutic approach is highly specific target cell entry. Therefore, I focus on the modification of the viral surface molecules that determine virus tropism by specific recognition of cellular receptors. Adenoviral fiber molecules protrude from the viral capsid and mediate attachment and entry. Measles virus H glycoproteins recognize host cell receptors, which is followed by cell entry via direct fusion. Both molecules will be engineered to target specific antigens unique for malignant melanoma. Retargeting of the virus is accomplished by the insertion of novel types of ligands into the binding region of the viral surface molecules. This is achieved against the background of ablated natural viral tropism by mutated motives necessary for natural host cell recognition.
The generation of these transductionally retargeted viruses will further improve our arsenal of virotherapeutic agents against malignant melanoma, but will also facilitate the targeting of virotherapy to other types of cancer due to the modular composition of the recombinant fiber and H proteins, respectively.
The measles virus project is a collaboration with the group of Dr. Guy Ungerechts at the National Centre for Tumor Diseases, Heidelberg.