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Recent Advances of Nanotechnologies for Cancer Immunotherapy Treatment
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
Besides these, many other immune checkpoint molecules are being investigated, including LAG3 (lymphocyte activation gene 3), TIM-3 (T-cell immunoglobulin domain and Mucin domain 3), KIR (killer-cell immunoglobulin-like receptor), B7-H3 (CD276), VISTA (V-domain Ig suppressor of T-cell activation), and so on. Recently, TIGIT (T-cell Ig and ITIM domain) was exploited that it can function as an immune checkpoint that mainly expressed on NK cell and T cells. When it binds to its ligand CD155 on APCs or target cells, the immune responses initiated by NK cells were significantly suppressed. The research demonstrated that blockade of TIGIT could restore the activity of tumor-infiltrating NK cells and enhance antitumor therapeutic effects. Furthermore, it can be incorporated with other ICB, such as PD-1 or PD-L1 to provide promising antitumor immunotherapy in future [231].
The roadmap towards cure of chronic hepatitis B virus infection
Published in Journal of the Royal Society of New Zealand, 2022
Although rapid inhibition of HBV antigen production by siRNAs and CAMs should help reconstitute HBV-specific immune responses, these may not be sufficient to reverse the T-cell exhaustion associated with life-long HBV infection. T cell effector function is inhibited in patients with chronic HBV infection by overexpression of inhibitory T cell receptors including PD1/PD-L1, CTLA-4, TIM-3, LAG-3, CD160, 2B4, TIGIT (Crawford and Wherry 2009; Chen et al. 2011; Boni, Barili, et al. 2019) Of these, PD-1 is the most highly expressed on HBV-specific T-cells within the liver of CHB patients whilst PD-L1 expression is increased on the hepatocytes (Liu et al. 2014). In woodchuck model, blockade of PD-L1 combined with DNA vaccination effectively controlled HBV viremia (Zhao et al. 2019). In patients with cancer, the new PD-1 and PD1 ligand inhibitors have been shown to restore antitumor activity of otherwise suppressed effector T cells and to improve survival. However, these checkpoint inhibitors are associated with an almost 10% incidence of immune-related adverse events (ir-AE), including autoimmune hepatitis, colitis and pneumonitis, which has raised concern about their use in patients with non-malignant diseases such as chronic HBV infection. In the first proof of concept study in CHB, a single dose of 0.3â mg/kg nivolumab (1/10 dose approved for cancer therapy) was safe and well-tolerated and led to HBsAg decline in 20/22 patients and sustained HBsAg loss in one patient (Gane, Verdon, et al. 2019). There are now multiple studies underway combining anti-PD1 with other new antiviral and immunomodulatory agents.