Enveloped virus resistant to complement inactivation for the treatment of cancer
A recombinant fusion protein is disclosed. The fusion protein comprises: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain. The fusion protein does not contain a GPI anchor. The fusion protein can be expressed with an N-terminal secretory signal peptide, which is cleaved to yield the mature protein on the surface of a cell line or an enveloped virus. An oncolytic virus expressing the fusion protein is resistant to complement inactivation and can be used to treat cancer.
1. A fusion protein comprising: (a) a CD55 peptide sequence comprising four short consensus repeats (SCR) of CD55, (b) a (G4S1)3 linker sequence C-terminal to the CD55 sequence, (c) a CD8 transmembrane domain C-terminal to the linker sequence, and (d) a CD8 intracellular domain C-terminal to the transmembrane domain wherein the CD8 intracellular domain is truncated; and wherein the fusion protein does not contain a GPI anchor.
2. The fusion protein of claim 1 , wherein the CD55 peptide sequence is a human CD55 peptide sequence.
3. The fusion protein of claim 1 , wherein the fusion protein further comprises a secretory signal peptide N-terminal to sequence (a).
4. The fusion protein of claim 3 , wherein the secretory signal peptide is a secretory signal peptide of CD55.
5. The fusion protein of claim 1 , having the sequence SEQ ID NO:2.
6. The fusion protein of claim 1 , having the sequence SEQ ID NO:3.
7. A nucleic acid encoding the fusion protein of claim 1 .
8. The nucleic acid of claim 7 , encoding a protein having the sequence SEQ ID NO:2.
9. The nucleic acid of claim 8 , having the sequence SEQ ID NO:1.
10. An expression vector comprising the nucleic acid of claim 7 , operatively linked to a control sequence.
11. A cell line stably expressing the fusion protein of claim 1 on the cell surface.
12. An enveloped virus incorporating the fusion protein of claim 1 on the virus membrane.
13. The virus of claim 12 , wherein the virus is an oncolytic virus.
14. A pharmaceutical composition comprising the virus of claim 13 and a pharmaceutically acceptable carrier.
15. A method for treating a neoplastic condition in a mammalian subject, comprising administering to the subject an amount of the virus of claim 12 effective to treat the condition.