Dostarlimab an Inhibitor of PD-1/PD-L1: A New Paradigm for the Treatment of Cancer

Abstract

Immunomodulation checkpoints usually adopted by healthy cells by tumors might cause an imbalance between host surveillance and tumor progression. Several tumors are incredibly resistant to standard treatment. The dynamic and long-lasting tumor regressions caused by antibodies targeting the PD-1/PD-L1 checkpoint have suggested a rebalancing of the host–tumor relationship. Checkpoint antibody inhibitors, like anti-PD-1/PD-L1, are unique inhibitors that reduce tumor growth by modulating the interaction between immune cells and tumor cells. These checkpoint inhibitors are swiftly emerging as a highly promising strategy for treating cancer because they produce impressive antitumor responses while having a limited number of adverse effects. Over the past several years, numerous checkpoint antibody inhibitors pointing to PD-1, PDL-1, and CTLA-4 have been available on the market. Despite its enormous success and usefulness, the anti-PD treatment response is restricted to certain kinds of cancer. This restriction can be attributed to the inadequate and diverse PD-1 expression in the tumor (MET) micro-environment. Dostarlimab (TSR-042), a drug that interferes with the PD-1/PD-L1 pathway, eliminates a crucial inhibitory response of an immune system and, as a result, has the potential to cause severe or deadly immune-mediated adverse effects. As cancer immunotherapy, dostarlimab enhances the antitumor immune response of the body.

The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

“…In recent years, immune checkpoint inhibitors (ICIs) have been shown to be one of the most promising and effective immunotherapies, which reconstitute anti-tumor responses and prevent tumor cells from evading immune surveillance by targeting specific molecules, such as programmed death receptor 1 (PD-1) or its ligand (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) 48 – 50 . Our current findings suggest that TOP2A is involved in regulating the expression of immune checkpoint (PD-L1) in NSCLC, and the upregulation of TOP2A significantly promotes the expression of immune checkpoint (PD-L1).…”

The role of TOP2A in immunotherapy and Vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

“…In recent years, immune checkpoint inhibitors (ICIs) have been shown to be one of the most promising and effective immunotherapies, which reconstitute anti-tumor responses and prevent tumor cells from evading immune surveillance by targeting speci c molecules, such as programmed death receptor 1 (PD-1) or its ligand (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) [52][53][54]. Our current ndings suggest that TOP2A is involved in regulating the expression of immune checkpoint (PD-L1) in NSCLC, and the upregulation of TOP2A signi cantly promotes the expression of immune checkpoint (PD-L1).…”

Anti-Tumor Potential of Post-Translational Modifications of PD-1

“…The FG ring of PD-1 is home to the sintilimab/PD-1 complex epitopes, according to structural analysis [ 79 ]. A humanized IgG4 kappa monoclonal antibody called dostarlimab attaches itself to the PD-1 receptor and prevents it from interacting with PD-L1 and PD-L2 [ 80 ]. The effectiveness of dostarlimab, zimberelimab [ 81 ], and sintilimab in modulating the post-translational modification of PD-1 has not yet been described.…”