Peer-Reviewed Publications

All Publications

Cross-Company Evaluation of the Human Lymphocyte Activation Assay

Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One in vitro assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the in vivo T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies.

Read more

Summary of a Workshop on Preclinical and Translational Safety Assessment of CD3 Bispecifics

Currently, there is a multitude of CD3 bispecifics with different molecular designs and binding properties in preclinical and clinical development for the treatment of liquid or solid tumors. The key safety concerns with CD3 bispecifics are excessive release of cytokines, which may translate to potentially life-threating cytokine release syndrome (CRS), target organ toxicity due to redirection of T-cells to normal tissues expressing the tumor-associated antigen (TAA) (off-tumor/on-target cytotoxicity), and, in some instances, neurotoxicity.

Read more

Cross-Site and Cross-Platform Variability of Automated Patch Clamp Assessments of Drug Effects on Human Cardiac Currents in Recombinant Cells

Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures affect the variability of IC50 values characterizing drug block potency. This impacts the utility of APC platforms for assessing a drug’s cardiac safety margin. We determined variability of APC data from multiple sites that measured blocking potency of 12 blinded drugs (with different levels of proarrhythmic risk) against four human cardiac currents (hERG [IKr], hCav1.2 [L-Type ICa], peak hNav1.5, [Peak INa], late hNav1.5 [Late INa]) with recommended protocols (to minimize variance) using five APC platforms across 17 sites.

Read more

An Evaluation Framework for New Approach Methodologies (NAMs) for Human Health Safety Assessment

The need to develop new tools and increase capacity to test pharmaceuticals and other chemicals for potential adverse impacts on human health and the environment is an active area of development. The response to these challenges for a “paradigm shift” toward using new approach methodologies (NAMS) for safety assessment has resulted in an explosion of initiatives by numerous organizations, but, for the most part, these have been carried out independently and are not coordinated in any meaningful way. To help remedy this situation, a framework that presents a consistent set of criteria, universal across initiatives, to evaluate a NAM’s fit-for-purpose was developed by a multi-stakeholder group of industry, academic, and regulatory experts.

Read more

Application of New Statistical Distribution Approaches for Environmental Mixture Risk Assessment: A Case Study

There is growing evidence that single substances present below their individual thresholds of effect may still contribute to combined effects. Here, the possible use of ecotoxicological threshold concentrations of no concern (i.e. 5th percentile of statistical distribution of ecotoxicological values) is investigated to fill data gaps in MRA.

Read more

WP_Query Object
(
    [query] => Array
        (
            [post_type] => publication
            [posts_per_page] => 5
            [type] => 
            [area] => 
            [committee] => 
            [authors] => true
            [showtitle] => 
            [meta_query] => Array
                (
                    [relation] => AND
                )

            [tax_query] => Array
                (
                )

            [paged] => 1
            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
        )

    [query_vars] => Array
        (
            [post_type] => publication
            [posts_per_page] => 5
            [type] => 
            [area] => 
            [committee] => 
            [authors] => true
            [showtitle] => 
            [meta_query] => Array
                (
                    [relation] => AND
                )

            [tax_query] => Array
                (
                )

            [paged] => 1
            [meta_key] => _ilsi_date
            [orderby] => meta_value
            [order] => DESC
            [error] => 
            [m] => 
            [p] => 0
            [post_parent] => 
            [subpost] => 
            [subpost_id] => 
            [attachment] => 
            [attachment_id] => 0
            [name] => 
            [pagename] => 
            [page_id] => 0
            [second] => 
            [minute] => 
            [hour] => 
            [day] => 0
            [monthnum] => 0
            [year] => 0
            [w] => 0
            [category_name] => 
            [tag] => 
            [cat] => 
            [tag_id] => 
            [author] => 
            [author_name] => 
            [feed] => 
            [tb] => 
            [meta_value] => 
            [preview] => 
            [s] => 
            [sentence] => 
            [title] => 
            [fields] => 
            [menu_order] => 
             => 
            [category__in] => Array
                (
                )

            [category__not_in] => Array
                (
                )

            [category__and] => Array
                (
                )

            [post__in] => Array
                (
                )

            [post__not_in] => Array
                (
                )

            [post_name__in] => Array
                (
                )

            [tag__in] => Array
                (
                )

            [tag__not_in] => Array
                (
                )

            [tag__and] => Array
                (
                )

            [tag_slug__in] => Array
                (
                )

            [tag_slug__and] => Array
                (
                )

            [post_parent__in] => Array
                (
                )

            [post_parent__not_in] => Array
                (
                )

            [author__in] => Array
                (
                )

            [author__not_in] => Array
                (
                )

            [ignore_sticky_posts] => 
            [suppress_filters] => 
            [cache_results] => 1
            [update_post_term_cache] => 1
            [lazy_load_term_meta] => 1
            [update_post_meta_cache] => 1
            [nopaging] => 
            [comments_per_page] => 50
            [no_found_rows] => 
        )

    [tax_query] => WP_Tax_Query Object
        (
            [queries] => Array
                (
                )

            [relation] => AND
            [table_aliases:protected] => Array
                (
                )

            [queried_terms] => Array
                (
                )

            [primary_table] => wp_11_posts
            [primary_id_column] => ID
        )

    [meta_query] => WP_Meta_Query Object
        (
            [queries] => Array
                (
                    [0] => Array
                        (
                            [key] => _ilsi_date
                        )

                    [relation] => OR
                )

            [relation] => AND
            [meta_table] => wp_11_postmeta
            [meta_id_column] => post_id
            [primary_table] => wp_11_posts
            [primary_id_column] => ID
            [table_aliases:protected] => Array
                (
                    [0] => wp_11_postmeta
                )

            [clauses:protected] => Array
                (
                    [wp_11_postmeta] => Array
                        (
                            [key] => _ilsi_date
                            [compare] => =
                            [compare_key] => =
                            [alias] => wp_11_postmeta
                            [cast] => CHAR
                        )

                )

            [has_or_relation:protected] => 
        )

    [date_query] => 
    [request] => SELECT SQL_CALC_FOUND_ROWS  wp_11_posts.ID FROM wp_11_posts  INNER JOIN wp_11_postmeta ON ( wp_11_posts.ID = wp_11_postmeta.post_id ) WHERE 1=1  AND ( 
  wp_11_postmeta.meta_key = '_ilsi_date'
) AND wp_11_posts.post_type = 'publication' AND (wp_11_posts.post_status = 'publish') GROUP BY wp_11_posts.ID ORDER BY wp_11_postmeta.meta_value DESC LIMIT 0, 5
    [posts] => Array
        (
            [0] => WP_Post Object
                (
                    [ID] => 22433
                     => 105
                     => 2020-03-23 12:14:51
                    [post_date_gmt] => 2020-03-23 17:14:51
                    [post_content] => 
                    [post_title] => Cross-Company Evaluation of the Human Lymphocyte Activation Assay
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => cross-company-evaluation-of-the-human-lymphocyte-activation-assay
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-03-23 12:21:37
                    [post_modified_gmt] => 2020-03-23 17:21:37
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=22433
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [1] => WP_Post Object
                (
                    [ID] => 22435
                     => 105
                     => 2020-03-23 12:24:53
                    [post_date_gmt] => 2020-03-23 17:24:53
                    [post_content] => 
                    [post_title] => Summary of a Workshop on Preclinical and Translational Safety Assessment of CD3 Bispecifics
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => summary-of-a-workshop-on-preclinical-and-translational-safety-assessment-of-cd3-bispecifics
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-03-23 12:24:53
                    [post_modified_gmt] => 2020-03-23 17:24:53
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=22435
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [2] => WP_Post Object
                (
                    [ID] => 22560
                     => 105
                     => 2020-03-27 10:15:21
                    [post_date_gmt] => 2020-03-27 15:15:21
                    [post_content] => 
                    [post_title] => Cross-Site and Cross-Platform Variability of Automated Patch Clamp Assessments of Drug Effects on Human Cardiac Currents in Recombinant Cells
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => cross-site-and-cross-platform-variability-of-automated-patch-clamp-assessments-of-drug-effects-on-human-cardiac-currents-in-recombinant-cells
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-03-27 10:15:21
                    [post_modified_gmt] => 2020-03-27 15:15:21
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=22560
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [3] => WP_Post Object
                (
                    [ID] => 22215
                     => 105
                     => 2020-02-06 13:06:39
                    [post_date_gmt] => 2020-02-06 18:06:39
                    [post_content] => 
                    [post_title] => An Evaluation Framework for New Approach Methodologies (NAMs) for Human Health Safety Assessment
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => an-evaluation-framework-for-new-approach-methodologies-nams-for-human-health-safety-assessment
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2020-02-06 13:06:39
                    [post_modified_gmt] => 2020-02-06 18:06:39
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=22215
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

            [4] => WP_Post Object
                (
                    [ID] => 21516
                     => 105
                     => 2019-08-01 08:23:24
                    [post_date_gmt] => 2019-08-01 13:23:24
                    [post_content] => 
                    [post_title] => Application of New Statistical Distribution Approaches for Environmental Mixture Risk Assessment: A Case Study
                    [post_excerpt] => 
                    [post_status] => publish
                    [comment_status] => closed
                    [ping_status] => closed
                    [post_password] => 
                    [post_name] => application-of-new-statistical-distribution-approaches-for-environmental-mixture-risk-assessment-a-case-study
                    [to_ping] => 
                    [pinged] => 
                    [post_modified] => 2019-08-01 08:23:59
                    [post_modified_gmt] => 2019-08-01 13:23:59
                    [post_content_filtered] => 
                    [post_parent] => 0
                    [guid] => https://hesiglobal.org/?post_type=publication&p=21516
                    [menu_order] => 0
                    [post_type] => publication
                    [post_mime_type] => 
                    [comment_count] => 0
                    [filter] => raw
                )

        )

    [post_count] => 5
    [current_post] => -1
    [in_the_loop] => 
    [post] => WP_Post Object
        (
            [ID] => 22433
             => 105
             => 2020-03-23 12:14:51
            [post_date_gmt] => 2020-03-23 17:14:51
            [post_content] => 
            [post_title] => Cross-Company Evaluation of the Human Lymphocyte Activation Assay
            [post_excerpt] => 
            [post_status] => publish
            [comment_status] => closed
            [ping_status] => closed
            [post_password] => 
            [post_name] => cross-company-evaluation-of-the-human-lymphocyte-activation-assay
            [to_ping] => 
            [pinged] => 
            [post_modified] => 2020-03-23 12:21:37
            [post_modified_gmt] => 2020-03-23 17:21:37
            [post_content_filtered] => 
            [post_parent] => 0
            [guid] => https://hesiglobal.org/?post_type=publication&p=22433
            [menu_order] => 0
            [post_type] => publication
            [post_mime_type] => 
            [comment_count] => 0
            [filter] => raw
        )

    [comment_count] => 0
    [current_comment] => -1
    [found_posts] => 400
    [max_num_pages] => 80
    [max_num_comment_pages] => 0
    [is_single] => 
    [is_preview] => 
    [is_page] => 
    [is_archive] => 
    [is_date] => 
    [is_year] => 
    [is_month] => 
    [is_day] => 
    [is_time] => 
    [is_author] => 
    [is_category] => 
    [is_tag] => 
    [is_tax] => 
    [is_search] => 
    [is_feed] => 
    [is_comment_feed] => 
    [is_trackback] => 
    [is_home] => 1
    [is_privacy_policy] => 
    [is_404] => 
    [is_embed] => 
    [is_paged] => 
    [is_admin] => 
    [is_attachment] => 
    [is_singular] => 
    [is_robots] => 
    [is_posts_page] => 
    [is_post_type_archive] => 
    [query_vars_hash:WP_Query:private] => de4cf155363bb0cb4a3137ee2f01341d
    [query_vars_changed:WP_Query:private] => 
    [thumbnails_cached] => 
    [stopwords:WP_Query:private] => 
    [compat_fields:WP_Query:private] => Array
        (
            [0] => query_vars_hash
            [1] => query_vars_changed
        )

    [compat_methods:WP_Query:private] => Array
        (
            [0] => init_query_flags
            [1] => parse_tax_query
        )

)