Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy

Feihu Wang; Dongqing Xu; Hao Su; Weijie Zhang; Xuanrong Sun; Maya K Monroe; Rami W Chakroun; Zongyuan Wang; Wenbing Dai; Richard Oh; Han Wang; Qin Fan; Fengyi Wan; Honggang Cui

doi:10.1126/sciadv.aaz8985

Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy

Sci Adv. 2020 Apr 29;6(18):eaaz8985. doi: 10.1126/sciadv.aaz8985. eCollection 2020 May.

Authors

Feihu Wang^{1

2}, Dongqing Xu³, Hao Su^{1

2}, Weijie Zhang^{1

2

4}, Xuanrong Sun^{1

5}, Maya K Monroe^{1

2}, Rami W Chakroun^{1

2}, Zongyuan Wang^{1

2}, Wenbing Dai^{1

2}, Richard Oh¹, Han Wang^{1

2}, Qin Fan^{1

2}, Fengyi Wan^{3

6

7}, Honggang Cui^{1

2

7}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Institute for NanoBiotechnology (INBT), Johns Hopkins University, Baltimore, MD 21218, USA.
³ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
⁴ Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁵ Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
⁶ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
⁷ Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Immune checkpoint blockers (ICBs) have shown great promise at harnessing immune system to combat cancer. However, only a fraction of patients can directly benefit from the anti-programmed cell death protein 1 (aPD1) therapy, and the treatment often leads to immune-related adverse effects. In this context, we developed a prodrug hydrogelator for local delivery of ICBs to boost the host's immune system against tumor. We found that this carrier-free therapeutic system can serve as a reservoir for extended tumoral release of camptothecin and aPD1 antibody, resulting in an immune-stimulating tumor microenvironment for boosted PD-1 blockade immune response. Our in vivo results revealed that this combination chemoimmunotherapy elicits robust and durable systemic anticancer immunity, inducing tumor regression and inhibiting tumor recurrence and metastasis. This work sheds important light into the use of small-molecule prodrugs as both chemotherapeutic and carrier to awaken and enhance antitumor immune system for improved ICBs therapy.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Publication types

Research Support, Non-U.S. Gov't