The therapeutic inhibition of immune checkpoints, including cytotoxic T lymphocyte-associated protein (CTLA)-4 and programmed cell death 1 (PD-1), through the use of function blocking antibodies can confer improved clinical outcomes by invigorating CD8(+) T cell-mediated anticancer immunity. However, low rates of patient responses and the high rate of immune-related adverse events remain significant challenges to broadening the benefit of this therapeutic class, termed immune checkpoint blockade (ICB). To overcome these significant limitations, controlled delivery and release strategies offer unique advantages relevant to this therapeutic class, which is typically administered systemically (e.g., intravenously), but more recently, has been shown to be highly efficacious using locoregional routes of administration. As such, in this paper, we describe an in situ crosslinked hydrogel for the sustained release of antibodies blocking CTLA-4 and PD-1 signaling from a locoregional injection proximal to the tumor site. This formulation results in efficient and durable anticancer effects with a reduced systemic toxicity compared to the bolus delivery of free antibody using an equivalent injection route. This formulation and strategy thus represent an approach for achieving the efficient and safe delivery of antibodies for ICB cancer immunotherapy.

Author Info: (1) Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. George W. Woodruff School of Mechanical E

Author Info: (1) Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. (2) Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. (3) Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USA. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr NW, Atlanta, GA 30332, USA and Emory University, 201 Dowman Drive, Atlanta, GA 30322, USA. Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Road NE, Atlanta, GA 30322, USA.