abstract |
The invention discloses a novel replication-type oncolytic adenovirus and its application that simultaneously blocks immune checkpoints PD-L1 and TIGIT. A soluble fusion protein of the present invention that simultaneously blocks immune checkpoints PD‑L1 and TIGIT and activates immune co-stimulatory pathways, characterized in that: the two ends of the soluble fusion protein are PD1 extracellular proteins that bind to PD‑L1, respectively. The region and the extracellular region of PVR bound to TIGIT, PD1 and PVR fragments are linked by a linker sequence, and the two ends of the soluble fusion protein can block the immune checkpoint PD-L1 and TIGIT at the same time after binding to PD-L1 and TIGIT respectively. Experiments show that the replicative oncolytic adenovirus Ad5sPD1PVR of the present invention can significantly block immune checkpoints and activate anti-tumor immunity, has significant anti-tumor activity, and has very high prospects and values for the development of anti-tumor drugs. |