Treatment of Colorectal Liver Metastases With Immunotherapy and Bevacizumab

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Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets Programmed Death-Ligand 1(PD-L1) and inhibits the interaction between PD-L1 and its receptors, Programmed cell Death protein 1(PD-1) and B7.1. Therapeutic blockade of PD-L1 binding by atezolizumab has been shown to enhanc...

Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets Programmed Death-Ligand 1(PD-L1) and inhibits the interaction between PD-L1 and its receptors, Programmed cell Death protein 1(PD-1) and B7.1. Therapeutic blockade of PD-L1 binding by atezolizumab has been shown to enhance the magnitude and quality of tumor specific T cell responses, resulting in improved anti tumor activity. Bevacizumab is a recombinant, humanized therapeutic antibody directed against vascular endothelial growth factor(VEGF). In addition to its well-characterized role in angiogenesis, VEGF is also believed to be involved in cancer immune evasion via the induction of myeloid- derived suppressor cells(MDSCs). These VEGF-induced MDSCs can suppress both T-cell and dendritic-cell function. Bevacizumab can restore and/or maintain the antigen presentation capacity of dendritic cells, leading to enhanced T-cell infiltration in tumors. When used in combination, VEGF targeting agents such as bevacizumab promote the normalization of tumor vasculature and may thereby increase access of therapeutic agents. Atezolizumab with bevacizumab, levoleucovorin, oxaliplatin, and 5-fluorouracil(FOLFOX). A translational study for renal cell carcinoma showed bevacizumab resulted in modulation of tumor immune microenvironment with Th1-related signatures, which was more potentiated by subsequent treatment with atezolizumab. This suggests potentiation of anti-tumor immunity with the combination of bevacizumab and atezolizumab.

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