Theranostics 2022; 12(10):4581-4598. doi:10.7150/thno.72310 This issue

Research Paper

Promising alternatives of CD47 monoclonal antibody: an injectable degradable hydrogel loaded with PQ912 for postoperative immunotherapy effectively blocks CD47-SIRPα signal

Chang Li1, Yubo Liu1, Dan Li1, Qiu Wang1, Shuang Zhou1, Haotian Zhang2, Yongjun Wang1, Zhonggui He1, Hongzhuo Liu1✉, Jin Sun1✉

1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.
2. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Li C, Liu Y, Li D, Wang Q, Zhou S, Zhang H, Wang Y, He Z, Liu H, Sun J. Promising alternatives of CD47 monoclonal antibody: an injectable degradable hydrogel loaded with PQ912 for postoperative immunotherapy effectively blocks CD47-SIRPα signal. Theranostics 2022; 12(10):4581-4598. doi:10.7150/thno.72310. Available from https://www.thno.org/v12p4581.htm

File import instruction

Abstract

Graphic abstract

Rationale: Many cancers have evolved different mechanisms to evade immune surveillance. Macrophages, the innate defense of the immune system, are limited in their phagocytosis by CD47 anti-phagocytic signaling expressed on the surface of tumor cells. Although the CD47 monoclonal antibody (aCD47) strategy has been extensively studied in clinical trials, the depletion of aCD47 by red blood cells (RBCs) and the resulting hematotoxicity have impeded their application in tumor treatment.

Methods: Here, we reported an injectable hydrogel scaffold that allowed for local delivery of small-molecule inhibitor PQ912. The biodegradable hydrogel scaffold (PQ/PB-Gel) was formed by rapid cross-linking of tetra-armed PEG succinimidyl succinate (Tetra-PEG-SS) solution and alkalescent bovine serum albumin (BSA) solution through ammonolysis reaction.

Results: PQ/PB-Gel had excellent effect on inhibiting local recurrence of two kinds of tumors. The hydrogel system inhibited the generation of “don't eat me” signals during the treatment cycle by inhibiting the expression of newly generated neoplastic CD47. Thus, it avoided adverse reactions such as erythrocytopenia after the use of aCD47 in terms of safety. After the “don't eat me” signal was blocked the clearance and recognition of cancer cells by macrophages and antigen-presenting cells were enhanced, sequentially systemic immune response was activated and further memory T lymphocyte (T cell) formation was induced.

Conclusions: PQ/PB-Gel had a simple preparation and administration method, low production cost, excellent efficacy and low toxicity, so it had good practicability. This might provide a safe alternative strategy for aCD47 for inhibit local tumor recurrence and distal metastasis in postoperative immunotherapy.

Keywords: PQ912, CD47-SIRPα, cancer immunotherapy, hydrogel scaffold, red blood cells