Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy.

Fibroblast activation protein (FAP) is a serine protease with dual enzymatic activities overexpressed in cancer-associated fibroblasts (CAFs) in several tumor types, while its expression in healthy adult tissues is scarce. FAP overexpression on CAFs is associated with poor prognosis and plays an important role in tumor development, progression, and invasion. Therefore, FAP is considered a robust therapeutic target for cancer therapy. Here, we try to review and highlight the recent advances in immunotherapies for FAP targeting including the anti-FAP antibodies and immunoconjugates, FAP chimeric antigen receptor (CAR)-T cell, and various FAP vaccines in a preclinical and clinical setting. Subsequently, a discussion on the challenges and prospects associated with the development and translation of effective and safe therapies for targeting and depletion of FAP is provided. We proposed that new CAR-T cell engineering strategies and nanotechnology-based systems as well as advanced functional biomaterials can be used to improve the efficiency and safety of CAR-T cells and vaccines against FAP for more personalized immunotherapy. This review emphasizes the immune targeting of FAP as an emerging stromal candidate and one of the crucial elements in immunotherapy and shows the potential for improvement of current cancer therapy. A summary of different immunotherapy approaches to target fibroblast activation protein (FAP) for cancer therapy.

The correlation between blood oxidative stress and sialic acid content in diabetic patients with nephropathy, hypertension, and hyperlipidemia.

This clinical study was designed to find out the correlation between oxidative stress and sialic acid (SA) content of plasma and RBCs in patients with type 2 diabetes. We evaluated SA concentration and oxidative stress biomarkers in healthy subjects and diabetic patients with and without complications in a cross-sectional survey. Significant changes in oxidative stress biomarkers and RBC-SA were revealed in the diabetic patients compared to those in the healthy group. Plasma SA significantly increased with an increase in lipid peroxidation of RBCs (LPO-RBC) (P < 0.001) in the diabetic patients without complication. RBC-SA significantly decreased with an elevation in LPO-RBC (P < 0.001) in all the diabetic patients and those with nephropathy. There was no significant correlation between plasma and RBC-SA and other oxidative stress biomarkers in the diabetic subjects. In multiple logistic regression analysis, RBC-SA was independently related to LPO-RBC in all the diabetic patients and those with nephropathy. We conclude that the induction of LPO-RBC in diabetic patients and those with nephropathy may influence the SA decomposition of RBC membrane, thereby altering its functions and transporter activities. Therefore, LPO-RBC and SA levels in RBCs can be used for prediction of diabetic nephropathy, and further studies to evaluate other factors contributing to desialylation of RBC membrane are justified.