Biomaterials: Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma

Abstract

Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments.

A.K. Kosmidesabce1R.A. Meyerade1J.W. HickeyabceK. AjebcK.N. CheungadJ.J. GreenadefghJ.P. Schneckbcei

a Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
b Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
c Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
d Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
e Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
f Department of Materials Science and Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
g Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
h Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
i Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA

 

Press Release by Johns Hopkins Medicine

http://www.sciencedirect.com/science/article/pii/S0142961216306639