A TVA-single-chain antibody fusion protein mediates specific targeting of a subgroup A avian leukosis virus vector to cells expressing a tumor-specific form of epidermal growth factor receptor.
We have previously described an approach that employs retroviral receptor-ligand bridge proteins to target retroviral vectors to specific cell types. To determine whether targeted retroviral entry can also be achieved using a retroviral receptor-single-chain antibody bridge protein, the TVA-MR1 fusion protein was generated. TVA-MR1 is comprised of the extracellular domain of the TVA receptor for subgroup A avian leukosis viruses (ALV-A), fused to the MR1 single-chain antibody that binds specifically to EGFRvIII, a tumor-specific form of the epidermal growth factor receptor. We show that TVA-MR1 binds specifically to a murine version of EGFRvIII and promotes ALV-A entry selectively into cells that express this cell surface marker. These studies demonstrate that it is possible to target retroviral vectors to specific cell types through the use of a retroviral receptor-single-chain antibody fusion protein.
Snitkovsky
S
S
Committee on Virology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Niederman
T M
TM
Carter
B S
BS
Mulligan
R C
RC
Young
J A
JA
D001354:Avian Leukosis Virus / Q000502:physiology*; D030161:Avian Proteins; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism*; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D011991:Receptors, Virus / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D030161:Avian Proteins; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C088745:Tva receptor; D066246:ErbB Receptors