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.
Claims28
-45. (canceled)
A Newcastle disease virus comprising a modified F protein cleavage sequence (FPCS), wherein the modified FPCS is selected from the group consisting of:
- S116:
- (SEQ ID NO:
- 1)
- 111H-N-R-T-K-S/F117;
- S116K:
- (SEQ ID NO:
- 2)
- 111H-N-K-T-K-S/F117;
- S116M:
- (SEQ ID NO:
- 3)
- 111H-N-R-M-K-S/F117;
- S116KM:
- (SEQ ID NO:
- 4)
- 111H-N-K-M-K-S/F-I118;
- and
- R116:
- (SEQ ID NO:
- 5)
- 111H-N-R-T-K-R/F-I118.
A method of inducing tumor regression in a subject, the method comprising contacting a tumor cell in the subject with a Newcastle disease virus comprising a modified F protein cleavage sequence (FPCS), wherein the modified FPCS is selected from the group consisting of:
- S116:
- (SEQ ID NO:
- 1)
- 111H-N-R-T-K-S/F117;
- S116K:
- (SEQ ID NO:
- 2)
- 111H-N-K-T-K-S/F117;
- S116M:
- (SEQ ID NO:
- 3)
- 111H-N-R-M-K-S/F117;
- S116KM:
- (SEQ ID NO:
- 4)
- 111H-N-K-M-K-S/F-I118;
- and
- R116:
- (SEQ ID NO:
- 5)
- 111H-N-R-T-K-R/F-I118.
A method of treating a neoplasia in a subject, the method comprising administering to the subject an effective amount of an attenuated Newcastle disease virus comprising a modified F protein cleavage sequence (FPCS), wherein the modified FPCS is selected from the group consisting of:
- S116:
- (SEQ ID NO:
- 1)
- 111H-N-R-T-K-S/F117;
- S116K:
- (SEQ ID NO:
- 2)
- 111H-N-K-T-K-S/F117;
- S116M:
- (SEQ ID NO:
- 3)
- 111H-N-R-M-K-S/F117;
- S116KM:
- (SEQ ID NO:
- 4)
- 111H-N-K-M-K-S/F-I118;
- and
- R116:
- (SEQ ID NO:
- 5)
- 111H-N-R-T-K-R/F-I118.
Dependencies are inferred from the claim text.