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-l igand 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 fusi on 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 MRI single-chain antibody that binds specifically to EGFRvIII, a tumor -specific form of the epidermal growth factor receptor. We show that TVA-MR 1 binds specifically to a murine version of EGFRvIII and promotes ALV-A ent ry selectively into cells that express this cell surface marker. These stud ies demonstrate that it is possible to target retroviral vectors to specifi c cell types through the use of a retroviral receptor-single-chain antibody fusion protein.