Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma-Reference-Cited by-同舟云学术

Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma

Published:2023-04-25 Issue:18 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Wang Feihu¹²³^ORCID,Huang Qian⁴^ORCID,Su Hao¹²,Sun Mingjiao¹²³^ORCID,Wang Zeyu¹,Chen Ziqi¹²,Zheng Mengzhen¹²,Chakroun Rami W.¹²,Monroe Maya K.¹²^ORCID,Chen Daiqing³,Wang Zongyuan¹²^ORCID,Gorelick Noah⁵,Serra Riccardo⁵,Wang Han¹²,Guan Yun⁴⁶^ORCID,Suk Jung Soo¹³⁶,Tyler Betty⁵,Brem Henry⁵⁷⁸⁹^ORCID,Hanes Justin¹³⁷⁸⁹,Cui Honggang¹²³⁹¹⁰^ORCID

Affiliation:

1. Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD 21218

2. Whiting School of Engineering, Institute for NanoBiotechnology, The Johns Hopkins University, Baltimore, MD 21218

3. Center for Nanomedicine, Wilmer Eye Institute, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231

4. Department of Anesthesiology and Critical Care Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205

5. Department of Neurosurgery, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231

6. Department of Neurological Surgery, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231

7. Department of Ophthalmology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231

8. Department of Biomedical Engineering, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231

9. Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231

10. Department of Materials Science and Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD 21218

Abstract

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic “don’t eat me” signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects.

Funder

Johns Hopkins University

HHS | NIH | National Institute of Neurological Disorders and Stroke

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2204621120

Reference58 articles.

1. Targeted therapy for brain tumours

2. Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme