Translatability of findings from cynomolgus monkey to human suggests a mechanistic role for IL-21 in promoting immunogenicity to an anti-PD-1/IL-21 mutein fusion protein.

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were only robust and exposure-impacting at the 2 lowest doses. At mid to high doses, ADA responses remained low magnitude and all subjects maintained exposure, despite most subjects developing ADA. Limited drug-specific IgE were also observed during the FIH study. ADA responses were not associated with any type of adverse event. The AMG 256 program represents a unique case where nonclinical studies informed on the risk of immunogenicity in humans, due to the IL-21-driven nature of the response.

Corrigendum: Translatability of findings from cynomolgus monkey to human suggests a mechanistic role for IL-21 in promoting immunogenicity to an anti-PD-1/IL-21 mutein fusion protein.

[This corrects the article DOI: 10.3389/fimmu.2024.1345473.].

Neutralizing Antibody Sample Testing and Report Harmonization.

Immunogenicity testing and characterization is an important part of understanding the immune response to administration of a protein therapeutic. Neutralizing antibody (NAb) assays are used to characterize a positive anti-drug antibody (ADA) response. Harmonization of reporting of NAb assay performance and results enables efficient communication and expedient review by industry and health authorities. Herein, a cross-industry group of NAb assay experts have harmonized NAb assay reporting recommendations and provided a bioanalytical report (BAR) submission editable template developed to facilitate agency filings. This document addresses key bioanalytical reporting gaps and provides a report structure for documenting clinical NAb assay performance and results. This publication focuses on the content and presentation of the NAb sample analysis report including essential elements such as the method, critical reagents and equipment, data analysis, study samples, and results. The interpretation of immunogenicity data, including the evaluation of the impact of NAb on safety, exposure, and efficacy, is out of scope of this publication.

The effects of meditation on individuals facing loneliness: a scoping review.

BACKGROUND: Meditation is defined as a mind and body practice focused on interactions between the brain, mind, body, and behaviour, containing four key elements: a quiet location with little distractions, a comfortable posture, a focus of attention, and an open attitude. We sought to review the benefits of meditation on the alleviation of loneliness. METHODS: A scoping review was conducted based on Arksey and O'Malley's five-stage framework. Eligibility criteria included primary studies of any type that investigated the effects of meditation on loneliness. Search strategies were developed and conducted on MEDLINE, EMBASE, AMED, and CINAHL. The National Center for Complementary and Integrative Health, and American Psychological Association websites were also searched. Articles meeting the inclusion criteria were critically reviewed using a descriptive-analytical narrative method. RESULTS: Thirteen studies met our inclusion criteria and were published between 2012 and 2020 across 10 countries. Eleven studies reported improvements in relation to loneliness. Of the remaining two studies (15%), one mentioned the alleviation of loneliness, but only looked primarily at social closeness in lonely individuals. The other study found a correlation between loneliness and nuclear factor (NF)-κB levels, which was the measured outcome; however, the direct effects of meditation on loneliness were unclear. Three main themes emerged from our analysis, as follows: 1) positive results across all studies, 2) relatively small randomized control trials conducted over the last decade, and 3) lack of diverse demographic information. CONCLUSIONS: While a small number of studies exist at this intersection, given all included studies indicated positive findings, the effects of meditation in alleviating loneliness are promising. Future research should be directed at understanding how meditation mitigates loneliness and how this intervention can impact practice for healthcare professionals.