Adenovirus armed with bispecific T cell activator
An adenovirus comprising a sequence of formula (I) 5′ITR-B 1 -B A -B 2 -B X -B B -B Y -B 3 -3′ITR wherein B Y comprises a transgene cassette containing four transgenes, said genes encoding a FAP-Bispecific T cell activator, CXL10, CXL9, and IFN. The disclosure also extends to a pharmaceutical composition comprising the virus, and use of the virus or formulation in treatment.
1. An adenovirus comprising a sequence of formula (I):
5′ITR-B 1 -B A -B 2 -B X -B B -B Y -B 3 -3′ITR (I)
wherein:
B 1 is a bond or comprises: E1A, E1B or E1A-E1B;
B A comprises: E2B-L1-L2-L3-E2A-L4;
B 2 is a bond or comprises: E3;
B X is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both;
B B comprises: L5;
B Y comprises: a transgene cassette comprising four transgenes, said transgenes encoding a FAP-bispecific T cell activator, CXCL10, CXCL9, and IFNα as shown in SEQ ID NO: 95 or a polynucleotide encoding the same amino acid sequence; and
B 3 is a bond or comprises: E4.
2. An adenovirus according to claim 1 , wherein the transgene cassette has a polynucleotide sequence shown in SEQ ID NO: 95.
3. An adenovirus according to claim 1 , wherein the adenovirus comprises SEQ ID NO: 84.
4. An adenovirus according to claim 1 , wherein the adenovirus is replication competent.
5. An adenovirus according to claim 1 , wherein the adenovirus is oncolytic.
6. An adenovirus according to claim 1 , wherein the virus has a hexon and fibre from Ad11.
7. A pharmaceutical composition comprising an adenovirus according to claim 1 and an excipient, diluent or carrier.
8. A method of treating a patient having a cancer of epithelial origin, comprising administering an adenovirus according to claim 1 , or a pharmaceutical composition according to claim 7 .
9. A method according to claim 8 , wherein the cancer is lung, breast, bladder, renal, or colorectal cancer.