Landscape of Subcutaneous Administration Strategies for Monoclonal Antibodies in Oncology.

In recent decades, subcutaneous (SC) administration of monoclonal antibodies (mAbs) has emerged as a promising alternative to intravenous delivery in oncology, offering comparable therapeutic efficacy while addressing patient preferences. This perspective article provides an in-depth analysis of the technological landscape surrounding SC mAb administration in oncology. It outlines various technologies under evaluation across developmental stages, spanning from preclinical investigations to the integration of established methodologies in clinical practice. Additionally, this perspective article explores emerging trends and prospective trajectories, shedding light on the evolving landscape of SC mAb administration. Furthermore, it emphasizes key checkpoints related to quality attributes essential for optimizing mAb delivery via the SC route. This review serves as a valuable resource for researchers, clinicians, and healthcare policymakers, offering insights into the advancement of SC mAb administration in oncology and its implications for patient care.

Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb. Seeking alternatives, physical polysaccharide hydrogels emerge as promising candidates due to their tunable physicochemical and biodegradability features. Unfortunately, none have demonstrated simultaneous biocompatibility, biodegradability, and controlled release properties for large proteins (≥150 kDa) after SC delivery in clinical settings. Here, a novel two-component hydrogel comprising chitosan and chitosan@DOTAGA is introduced that can be seamlessly mixed with sterile mAbs formulations initially designed for intravenous (IV) administration, repurposing them as novel tunable SC formulations. Validated in mice and nonhuman primates (NHPs) with various mAbs, including trastuzumab and rituximab, the hydrogel exhibited biodegradability and biocompatibility features. Pharmacokinetic studies in both species demonstrated tunable controlled release, surpassing the capabilities of rHuPH20, with comparable parameters to the rHuPH20+mAbs formulation. These findings signify the potential for rapid translation to human applications, opening avenues for the clinical development of this novel SC biosimilar formulation.