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

Feihu Wang; Qian Huang; Hao Su; Mingjiao Sun; Zeyu Wang; Ziqi Chen; Mengzhen Zheng; Rami W Chakroun; Maya K Monroe; Daiqing Chen; Zongyuan Wang; Noah Gorelick; Riccardo Serra; Han Wang; Yun Guan; Jung Soo Suk; Betty Tyler; Henry Brem; Justin Hanes; Honggang Cui

doi:10.1073/pnas.2204621120

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

Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2204621120. doi: 10.1073/pnas.2204621120. Epub 2023 Apr 25.

Authors

Feihu Wang^{1

2

3}, Qian Huang⁴, Hao Su^{1

2}, Mingjiao Sun^{1

2

3}, Zeyu Wang¹, Ziqi Chen^{1

2}, Mengzhen Zheng^{1

2}, Rami W Chakroun^{1

2}, Maya K Monroe^{1

2}, Daiqing Chen³, Zongyuan Wang^{1

2}, Noah Gorelick⁵, Riccardo Serra⁵, Han Wang^{1

2}, Yun Guan^{4

6}, Jung Soo Suk^{1

3

6}, Betty Tyler⁵, Henry Brem^{5

7

8

9}, Justin Hanes^{1

3

7

8

9}, Honggang Cui^{1

2

3

9

10}

Affiliations

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.

Keywords: cancer; chemotherapy; hydrogel; immunotherpay; self-assembly.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / drug therapy
Cell Line, Tumor
Glioblastoma* / drug therapy
Glioblastoma* / pathology
Humans
Hydrogels / therapeutic use
Immunotherapy / methods
Neoplasm Recurrence, Local / drug therapy
Paclitaxel
Tumor Microenvironment
Tumor-Associated Macrophages / pathology

Substances

Paclitaxel
Hydrogels

Abstract

Publication types

MeSH terms

Substances

Grants and funding