Miniaturization of hiPSC-derived 3D neural cultures in stirred-tank bioreactors for parallelized preclinical assessment of rAAV.

Engineered 3D models employing human induced pluripotent stem cell (hiPSC) derivatives have the potential to recapitulate the cell diversity and structure found in the human central nervous system (CNS). Therefore, these complex cellular systems offer promising human models to address the safety and potency of advanced therapy medicinal products (ATMPs), such as gene therapies. Specifically, recombinant adeno-associated viruses (rAAVs) are currently considered highly attractive for CNS gene therapy due to their broad tropism, low toxicity, and moderate immunogenicity.

Immune microenvironment dynamics of HER2 overexpressing breast cancer under dual anti-HER2 blockade.

Introduction: The clinical prognosis of the HER2-overexpressing (HER2-OE) subtype of breast cancer (BC) is influenced by the immune infiltrate of the tumor. Specifically, monocytic cells, which are promoters of pro-tumoral immunosuppression, and NK cells, whose basal cytotoxic function may be enhanced with therapeutic antibodies. One of the standards of care for HER2 BC patients includes the combination of the anti-HER2 antibodies trastuzumab and pertuzumab.

Capturing the third dimension in drug discovery: Spatially-resolved tools for interrogation of complex 3D cell models.

Advanced three-dimensional (3D) cell models have proven to be capable of depicting architectural and microenvironmental features of several tissues. By providing data of higher physiological and pathophysiological relevance, 3D cell models have been contributing to a better understanding of human development, pathology onset and progression mechanisms, as well as for 3D cell-based assays for drug discovery. Nonetheless, the characterization and interrogation of these tissue-like structures pose major challenges on the conventional analytical methods, pushing the development of spatially-resolved technologies.