Replication-enhanced oncolytic adenoviruses
View Patent ↗Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.
1. An adenovirus vector, wherein the adenovirus vector comprises:
a. a CMV promoter/enhancer inserted in a noncoding region upstream of the adenovirus E1 coding region;
b. a SV40 promoter/enhancer inserted in the adenovirus E3 region;
c. a deletion in part or all of the E3 coding region;
d. a E1A gene comprising a delta-24 deletion;
e. a E1B 55K deletion;
f. wherein the CMV promoter/enhancer is operably linked to a heterologous nucleic acid sequence encoding MEM40; and
g. wherein the SV40 promoter/enhancer is operably linked to a heterologous nucleic acid sequence encoding IFNβ.
2. The adenovirus vector of claim 1 , wherein the adenovirus is serotype 5.
3. The adenovirus vector of claim 1 , wherein the CMV promoter/enhancer is located between the left inverted terminal repeat (ITR) and 5′-end of the functional E1A region.
4. The adenovirus vector of claim 1 , wherein the SV40 promoter/enhancer is located between the E3 12.5K and E3 RID-alpha regions.
5. The adenovirus vector of claim 1 , wherein
a. the CMV promoter/enhancer comprises the nucleotide sequence of SEQ ID NO: 1; and
b. the SV40 promoter/enhancer comprises the nucleotide sequence of SEQ ID NO: 2.
6. The adenovirus vector of claim 1 , wherein the CMV promoter/enhancer comprises the nucleotide sequence of SEQ ID NO: 1.
7. The adenovirus vector of claim 1 , wherein the SV40 promoter/enhancer comprises the nucleotide sequence of SEQ ID NO: 2.