HESI workshop summary: Interpretation of developmental and reproductive toxicity endpoints and the impact on data interpretation of adverse events.

The Health and Environmental Sciences Institute Developmental and Reproductive Toxicology (HESI-DART) group held a hybrid in-person and virtual workshop in Washington, DC, in 2022. The workshop was entitled, "Interpretation of DART in Regulatory Contexts and Frameworks." There were 154 participants (37 in person and 117 virtual) across 9 countries.

Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors.

Background: Chimeric antigen receptor (CAR) T cell therapy has proven its clinical utility in hematological malignancies. Optimization is still required for its application in solid tumors. Here, the lack of cancer-specific structures along with tumor heterogeneity represent a critical barrier to safety and efficacy.

Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners.

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable response rates and revolutionized the treatment of patients suffering from defined hematological malignancies. However, many patients still do not respond to this therapy or relapse after an initial remission, underscoring the need for improved efficacy. Insufficient in vivo activity, persistence, trafficking, and tumor infiltration of CAR T cells, as well as antigen escape and treatment-associated adverse events, limit the therapeutic success.

Postnatal Hepatobiliary and Gastrointestinal Systems Development and Impact on ADME.

Toxicity can result from variable target organ sensitivity and exposure based on postnatal development. Changes in the gastrointestinal tract (GIT) in neonates are driven by initial enteral feedings. These are important for nutrient uptake as well as drug disposition and include motility, expansion of enzyme and transporter function, permeability, intestinal microbiome, and species-specific maturation.

A Simple and Effective Flow Cytometry-Based Method for Identification and Quantification of Tissue Infiltrated Leukocyte Subpopulations in a Mouse Model of Peripheral Arterial Disease.

Arteriogenesis, the growth of a natural bypass from pre-existing arteriolar collaterals, is an endogenous mechanism to compensate for the loss of an artery. Mechanistically, this process relies on a locally and temporally restricted perivascular infiltration of leukocyte subpopulations, which mediate arteriogenesis by supplying growth factors and cytokines. Currently, the state-of-the-art method to identify and quantify these leukocyte subpopulations in mouse models is immunohistology.