Novel replicating oncolytic adenovirus capable of simultaneously inhibiting immune checkpoints of PD-L1 (programmed cell death ligand 1) and TIGIT (T cell immunoreceptor with Ig (immune globulin) and ITIM (immunoreceptor tyrosine-based inhibition motif) domain) and application thereof

Abstract

The invention discloses a novel replicating oncolytic adenovirus capable of simultaneously inhibiting immune checkpoints of PD-L1 and TIGIT and application thereof. According to the novel replicatingoncolytic adenovirus capable of simultaneously inhibiting immune checkpoints of PD-L1 and TIGIT, a soluble fusion protein capable of simultaneously inhibiting immune checkpoints of PD-L1 and TIGIT andactivating immune costimulatory pathways is characterized in that both ends of the soluble fusion protein are a PD1 (programmed cell death protein 1) extracellular region for binding PD-L1 and a PVR(poliovirus receptor) extracellular region for binding TIGIT respectively, PD1 fragments and PVR fragments are connected through a linker sequence, and both ends of the soluble fusion protein can simultaneously inhibiting the immune checkpoints of PD-L1 and TIGIT after binding PD-L1 and TIGIT respectively. Experiments show that the novel replicating oncolytic adenovirus (ad5sPD1PVR) can significantly inhibit the immune checkpoints and activate antitumor immunity effects, achieve significant antitumor activity and accordingly have a good prospect and high values for developing antitumor drugs.

Description

technical field [0001] The present invention relates to the fields of oncolytic virus therapy and tumor immune checkpoint blockade therapy, in particular to a novel replication-type oncolytic adenovirus that simultaneously blocks immune checkpoints PD-L1 and TIGIT and its application. Background technique [0002] Cancer is one of the most harmful diseases to human life and health. More than 8 million people die from cancer every year in the world, and the number of new cancer patients is still increasing every year. At present, all traditional tumor treatment methods, including surgery, radiotherapy and chemotherapy, have limitations, and the market urgently needs new and effective treatment methods. [0003] With the emerging exciting clinical research results, anti-tumor immunotherapy has brought hope to cancer patients. However, during the occurrence and development of tumors, they not only avoid immune attacks by hiding themselves (lack of antigen molecules recognized ...

AI Technical Summary

Problems solved by technology

We imagine whether oncolytic virus immunotherapy can make tumors more sensitive to treatments targeting immune checkpoints, thereby solving the problem of low universality (efficiency) of immune checkpoint therapy (the problem encountered by immune checkpoint therapy) 1st question)

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