The invention relates to an
oncolytic virus VSV-aPDL1 / aCD137 for expressing a
bispecific antibody as well as a construction method and application of the
oncolytic virus VSV-aPDL1 / aCD137. The preparation method comprises the following steps: firstly designing aPDL1 / aCD137, then synthesizing an aPDL1 / aCD137
gene in vitro, amplifying the aPDL1 / aCD137
gene, connecting the aPDL1 / aCD137
gene to a pT7-VSV whole
genome plasmid to obtain a
virus whole
genome plasmid pT7-VSV-aPDL1 / aCD137, and then co-transfecting the
plasmid and a helper plasmid to a 293
T cell to obtain the VSV-aPDL1 / aCD137
oncolytic virus. According to the present invention, the local anti-tumor immune response of the tumor is activated through the
virus, the infiltration of the
lymphocyte to the
tumor tissue is recruited, the anti-PD-L1 / anti-CD137
bispecific antibody is expressed, the inhibition of the PD-1 / PD-L1 pathway on the
T cell is blocked, and the inhibition
signal of the PD-1 / PD-L1 pathway on the tumor
cell surface is reversed into the CD137
signal of the activated
T cell, such that the
functional failure of the T
cell caused by the PD-1 / PD-L1 pathway can be blocked, and the anti-tumor immune response of the tumor can be inhibited; the function and viability of T cells can be further improved, long-term immune surveillance on tumors is realized, and long-acting anti-tumor immune response is generated. Experiments show that the oncolytic
virus can significantly prolong the lifetime of tumor-bearing mice, and a new strategy is provided for development of
solid tumor drugs.