Analisis CAR, NPL, BOPO dan LDR terhadap Profitabilitas

This research aimed to examine the effect of Capital Adequacy Ratio (CAR), Non Performing Loan (NPL),Operating Expenses Operating Income (BOPO) and Loan to Deposite Ratio (LDR) ratios on profitability (ROA). This type of research is quantitative research. The sample selection method in this research used purposive sampling method. The sample used was 20 of 45 banking companies listed on the Indonesia Stock Exchange with the periode 2016-2020. The analytical method used was multiple linear regression analysis using the SPSS version 22 program. The result showed that the Capital Adequacy Ratio (CAR) t test had a significant effect on profitability (ROA) partially, Operating Expenses Operating Income (BOPO) has a negative effect on profitability(ROA) partially, then Non Performing Loan (NPL) and Loan to Deposite Ratio (LDR) have a positive and not significant effect on profitability (ROA). And from the result of the f test, the Capital Adequacy Ratio (CAR), Non Performing Loan (NPL), Operating Expenses Operating Income (BOPO) and Loan to Deposite Ratio (LDR) variables have a simultaneous effect on profitability (ROA). Keywords: CAR, NPL, BOPO, LDR, ROA

Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance anti-HIV activity in vitro

HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4+ T cells that express virus either spontaneously or after intentional latency reversal. However, the T-cell exhaustion and the patient-specific autologous paradigm of CAR-T hurdled the clinical application. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 CAR (3BE CAR) construct that enables the expression of PD-1 blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV envelope glycoprotein (Env). In comparison with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater anti-HIV potency with stronger proliferation capability, higher killing efficiency (up to ~75%) and enhanced cytokine secretion in the presence of HIV envelope glycoprotein-expressing cells. Furthermore, our approach achieved high levels (over 97%) of the TCR-deficient 3BE CAR-T cells with the functional inactivation of endogenous TCR to avoid graft-versus-host disease without compromising their antiviral activity relative to standard anti-HIV CAR-T cells. These data suggest that we have provided a feasible approach to large-scale generation of "off-the-shelf" anti-HIV CAR-T cells in combination with antibody therapy of PD-1 blockade, which can be a powerful therapeutic candidate for the functional cure of HIV.

Modeling predicts differences in CAR T cell signaling due to biological variability

In recent decades, chimeric antigen receptors (CARs) have been successfully used to generate engineered T cells capable of recognizing and eliminating cancer cells. The structure of CARs frequently includes costimulatory domains, which enhance the T cell response upon antigen encounter. However, it is not fully known how the CAR co-stimulatory domains influence T cell activation in the presence of biological variability. In this work, we used mathematical modeling to elucidate how the inclusion of one such co-stimulatory molecule, CD28, impacts the response of a population of engineered T cells under different sources of variability. Particularly, our simulations demonstrate that CD28-bearing CARs mediate a faster and more consistent population response under both target antigen variability and kinetic rate variability. We identify kinetic parameters that have the most impact on mediating cell activation. Finally, based on our findings, we propose that enhancing the catalytic activity of lymphocyte-specific protein tyrosine kinase (LCK) can result in drastically reduced and more consistent response times among heterogeneous CAR T cell populations.