trastuzumab (BP 02 / BP02)

Sequential Switching Versus Combinatorial Blockade: Navigating the Safety-Efficacy Balance of Biologics in SLE.

Hsu Teng-Chieh TC, Wei James Cheng-Chung JC

Oesophageal tissue screening system for assessing the retention and mucosal absorption of biologics.

Karavasili Christina C, Young Thomas T, Chan Alvin A, Lal Nikhil N et al.

Drug delivery to the oesophagus poses unique challenges, including rapid transit time due to gravity and the presence of a stratified squamous non-keratinized epithelium. Here, to rapidly identify formulations of excipients for enhanced drug delivery to the oesophagus, we developed an oesophageal tissue screening system consisting of specialized custom plates, to incorporate gravity effects, and excised oesophageal mucosa tissues. Using the screening system, we built an excipient library identifying the most effective non-toxic permeation enhancers and selected the formulation that could prolong the retention on the oesophageal mucosa. We identified an absorption enhancer that resulted in a 876-fold increase in the oesophageal transport of a model drug (4 kDa) in pig tissue. We validated this formulation in human oesophageal tissue and in vivo in pigs with the model drug and infliximab (149 kDa), demonstrating enhanced permeability. We characterized the mechanism of the approach, noting its capacity for enhanced delivery without causing cellular disruption of the oesophageal tissue. The oesophageal tissue screening system shows promise for high-throughput screening of effective oesophageal drug delivery systems.

Immune Checkpoint Inhibitor-Associated Autoimmune Bullous Disease: A Clinical Review.

Nukaly Houriah Y HY, Barnawi Ghassan G, Thalib Husna Irfan HI, Basamih Khalid Abdulrahman KA et al.

Immune checkpoint inhibitors (ICIs) have markedly advanced oncology by enhancing the immune system's ability to combat malignancies. However, their use is increasingly associated with immune-related adverse events, including immunobullous dermatoses. These disorders, such as bullous pemphigoid, pemphigus vulgaris, linear immunoglobulin A bullous dermatosis, mucous membrane pemphigoid, paraneoplastic pemphigus, dermatitis herpetiformis, and lichen planus pemphigoides present significant diagnostic and therapeutic challenges. This clinical review explores the pathogenesis, clinical presentation, diagnosis, and management strategies of immunobullous dermatoses triggered by ICIs, highlighting the complex relationship between effective cancer treatment and immune regulation. ICI-induced immunobullous dermatoses closely mimic their conventional autoimmune counterparts but often have unique clinical considerations, such as delayed onset, mucosal predilection, and persistence post-discontinuation of medication. Diagnostic evaluation relies on clinical suspicion, histopathology, direct and indirect immunofluorescence, and enzyme-linked immunosorbent assays. Management typically involves corticosteroids and immunosuppressants, with biologics such as rituximab, dupilumab and omalizumab reserved for refractory cases. Decisions regarding the continuation of ICIs require individualized assessment, balancing cancer control with autoimmune toxicity. Dermatologic and oncologic teams must navigate dual priorities of mitigating autoimmune toxicity and preserving oncologic benefit.

Quantitative live-imaging platform to probe the spatio-temporal internalization and lysosomal degradation of therapeutic antibodies and ADCs in cells.

Jain Nikhil N, Tiwari Atul A, Gupta Manoj Kumar MK, Namboodiri Devika C DC et al.

The therapeutic efficacy of antibody-drug conjugates (ADCs) is governed not only by target binding but also by the efficiency of receptor-mediated internalization, intracellular trafficking, and lysosomal degradation. However, most conventional assays provide static or endpoint measurements, limiting their ability to resolve these dynamic, multistep processes. Here, we report a quantitative, dual-probe live-cell imaging platform that simultaneously tracks antibody internalization and lysosomal degradation with spatiotemporal resolution. By combining an internalization tracer with a cathepsin-activated fluorogenic sensor, this assay enables direct, real-time measurement of lysosomal routing following cellular uptake. Using trastuzumab and clinically approved HER2-targeting ADCs as model systems, we demonstrate that internalization and lysosomal degradation are temporally uncoupled and occur with distinct kinetics. Moreover, ADCs sharing the same antibody backbone exhibited markedly different processing profiles, highlighting the influence of linker chemistry and payload properties on their intracellular fate. These results underscore the importance of evaluating ADCs as integrated molecular systems rather than as modular components. This platform provides a scalable and mechanistically informative tool for ADC development, enabling candidate ranking, linker screening, and rational payload - linker optimization based on functional intracellular behavior rather than uptake alone. As such, it offers a framework for data-driven design of next-generation ADCs with improved therapeutic index.