immunotherapy

The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missinmore...

Prolgolimab is an IgG1 anti–PD-1 (programmed cell death protein 1) monoclonal antibody containing the Fc-silencing ‘LALA’ mutation. We assessed the efficacy and safety of two dosing regimens of prolgolimab in patients with advanced melanoma in a multicenter open-label parallel-arm phase II trial (MIRACULUM). We present the final analysis after 1 year of follow-up and additional efficacy results from 2 years of follow-up.

PD-1/PD-L1-based therapy has been named a revolution in cancer treatment. By the end of 2018, more than 100 anti-PD-1 and anti-PD-L1 antibodies were in various stages of development, and more than 2000 clinical trials with their use have been registered. Characterization of such antibodies requires a bioassay to determine their biological activity. In this study, we developed a cell-based bioassay for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies. We chose reporter system consisting of two cell lines and compared several approaches for activation of effector cell line based on superantigens, soluble anti-CD3 antibodies, transmembrane anti-CD3 antibodies, chimeric antigenic receptors (CARs) and bispecific T-cell engager antibodies. The bispecific T-cell engager antibodies offer several advantages over the other approaches. We characterized the bioassay and demonstrated its applicability for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies. The proposed bioasmore...

This review focuses on the structure and molecular action mechanisms of chimeric antigen receptors (CARs) and major aspects of the manufacturing and clinical application of products for the CAR-T (CAR-modified T lymphocyte) therapy of hematological and solid tumors with special emphasis on the strategies for combined use of CAR-T therapy with immuno-oncological monoclonal antibodies (checkpoint inhibitors) and cytokines to boost survival, persistence, and antitumor efficacy of CAR-T therapy. The review also summarizes preclinical and clinical data on the additive effects of the combined use of CAR-T therapy with interleukins and monoclonal antibodies targeting immune checkpoints.