Compositions featuring an attenuated Newcastle disease virus and methods of use for treating neoplasia
AssigneeMedImmune, LLC
InventorsXing Cheng, Danielle Carroll, Matthew McCourt, Mark Galinski, Hong Jin
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Abstract
The present invention provides methods for inducing regression of tumors in human subjects, the methods utilize a modified mesogenic strain of Newcastle disease virus (NDV) with modified F protein cleavage site, which is non-pathogenic to poultry (lentogenic), but exhibits oncolytic properties. The disclosed methods provide safe, effective and reliable means to induce regression of a tumor in an individual in need thereof. These methods overcome the drawbacks of using pathogenic strains of viruses for human therapy.
Claims20
An attenuated Newcastle disease virus (NDV) 73T strain comprising an F protein cleavage site derived from glycoprotein B (gB) of cytomegalovirus (CMV), wherein the F protein cleavage site comprises a modified F protein cleavage sequence (FPCS) comprising R116:
- 111H-N-R-T-K-R/F-I118 (SEQ ID NO:
- 5) and wherein the virus further comprises an increased HN-L intergenic region consisting of a non-coding sequence of 198 or 318 nt in length.
A nucleic acid comprising the full length cDNA of 73T, wherein the nucleic acid encodes a modified F protein cleavage sequence selected from the group consisting of:
- S116:
- 111H-N-R-T-K-S/F117
- (SEQ ID NO:
- 1);
- S116K:
- 111H-N-K-T-K-S/F117
- (SEQ ID NO:
- 2);
- S116M:
- 111H-N-R-M-K-S/F117
- (SEQ ID NO:
- 3);
- S116KM:
- 111H-N-K-M-K-S/F-I118
- (SEQ ID NO:
- 4);
- and
- R116:
- 111H-N-R-T-K-R/F-I118
- (SEQ ID NO:
- 5).
A vector comprising full length cDNA of 73T, wherein the vector encodes a modified F protein cleavage sequence selected from the group consisting of:
- S116:
- 111H-N-R-T-K-S/F117
- (SEQ ID NO:
- 1);
- S116K:
- 111H-N-K-T-K-S/F117
- (SEQ ID NO:
- 2);
- S116M:
- 111H-N-R-M-K-S/F117
- (SEQ ID NO:
- 3);
- S116KM:
- 111H-N-K-M-K-S/F-I118
- (SEQ ID NO:
- 4);
- and
- R116:
- 111H-N-R-T-K-R/F-I118
- (SEQ ID NO:
- 5).
Dependencies are inferred from the claim text.