Srikanth Reddi

Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.

Australian Mineral Industries Research Association P9 project developed a methodology to conduct gas dispersion measurements (such as superficial gas velocity, gas hold-up and bubble size) in industrial flotation celts. These measurements are used to calculate the bubble surface area flux, which has a strong relationship with cell recovery. JKTech conducted gas dispersion measurements on the Stream II lead flotation circuit at Rampura Agucha Mine as part of an optimisation study. Superficial gas velocity profiles were used in simulations (using JKSimFloat software) to provide guidance for the potential circuit improvements. Simulation results showed that the galena grade could be improved by 1.7% white maintaining similar lead and silver recoveries in the final lead concentrate. The optimum superficial gas velocity profile from simulations was implemented in the Stream II lead flotation circuit and the results were compared with the previous plant data. It was shown that the lead circuit achieved a 2% grade improvement in the final lead concentrate.