Tumor immunotherapy antibody fusion protein BY24.3 IPR: Dual-targeted fusion protein targeting PD1 or PD-L1 and targeting the VEGF family and its use (Patent Application No. 201710905683.9, PCT/CN2018/10674)

The effectiveness of PD1/PD-L1 combination anti-angiogenic therapy may be based on the fact that: Improve the efficacy of PD1/PD-L1 monoclonal antibody by blocking the immunosuppressive effects of VEGF and promoting T-cell infiltration in tumour tissue. Drugs acting on the VEGF target effectively "modulate" the normalisation of tumour neovascularisation and improve the immune "desertification" of tumour tissue due to abnormal neovascularisation.

The bifunctional antibody binds with high affinity to multiple targets including PD1, VEGF-A and VEGF-B, and has a higher affinity for VEGF-A than bevacizumab (AVASTIN).

· Research results on BY24.3, an antibody fusion protein for tumour immunotherapy

Results of the in vivo study of BY24.3

The expression vector has been constructed; stable cells have been screened; the expression amount has reached more than 1.5g/L; the affinity with PD1 is 2.80×10-9M and the affinity with VEGF-A is 3.98×10-12M; the tumor suppression effect in transgenic mice is better than the  new drug Opdivo (Nivolumuab), which is marketed overseas. And the animals have good safety, with no abnormalities. PDX models (clinical samples) of colorectal cancer, lung cancer and liver cancer completed by IDMO showed good tumour suppression effect in combination with chemotherapy drugs.