Supramolecular peptide hydrogel epitope vaccine functionalized with CAR-T cells for the treatment of solid tumors

Pengxiang Yang; Xiaomin Yao; Xue Tian; Yuehan Wang; Leilei Gong; Yumin Yang; Jing Jie

doi:10.1016/j.mtbio.2025.101517

Supramolecular peptide hydrogel epitope vaccine functionalized with CAR-T cells for the treatment of solid tumors

Pengxiang Yang^* (Co-first Author), Xiaomin Yao (Co-first Author), Xue Tian, Yuehan Wang, Leilei Gong^*, Yumin Yang^*, Jing Jie^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

3 Citations (Scopus)

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy, which benefits from the perfect combination of gene editing techniques and antibody engineering, has shown outstanding clinical efficacy in hematological malignancies. Solid tumors present the next challenge due to their extremely complicated microenvironment and structural characteristics. Targeting efficiency and persistence are currently bottleneck issues in the clinical treatment of CAR-T. Beyond drugs and cytokines, biomaterials can modulate the immune response, assisting adoptive CAR-T cells in exerting their function. In this study, a supramolecular peptide hydrogel epitope vaccine was designed to serve as both a preparation medium and a reservoir for CAR-T cells. The self-assembling peptide formed a nanofiber scaffold through non-covalent interactions of amphiphilic amino acids and ion stabilizers. Firstly, the complementary peptide conjugated vaccine epitopes and CAR-T target sites were derived from different extracellular domains of the HER2 protein, and the combination treatment improved tumor antigen spreading and targeting efficiency. The epitope hydrogel promoted CAR-T cell proliferation, cytotoxic activity, and lymphocyte subpopulation transformation. Furthermore, the supramolecular peptide epitope vaccine encapsulated CAR-T (SPEV-CAR-T) induced endogenous humoral and cellular immune responses through a sustained release of the hydrogel and CAR-T cells, demonstrating superior anti-tumor effects in an in vivo mouse model. Most importantly, SPEV-CAR-T induced central memory cells in systemic immune tissues, addressing the poor persistence of single CAR-T therapy. The integration and complementation of active and passive immune responses in this all-in-one hydrogel epitope vaccine and CAR-T system facilitated a sequential succession of endogenous and exogenous immune responses, promoting persistent and specific tumor attack. SPEV-CAR-T showed superior therapeutic effects in solid tumors. © 2025 The Authors.

Original language	English
Article number	101517
Journal	Materials Today Bio
Volume	31
Online published	22 Jan 2025
DOIs	https://doi.org/10.1016/j.mtbio.2025.101517
Publication status	Published - Apr 2025
Externally published	Yes

Funding

We want to acknowledge the financial support received from the National Key R&D Program of China (No.2022YFC2409800, 2022YFC2409802), National Natural Science Foundation of China (No. 32271389, 32230057, 31900987), Jiangsu Natural Science Foundation (No. BK20230608), Nantong Science and Technology Plan Project (No.MSZ2022196), Nantong University innovative training program (No.2024007CX).

Research Keywords

Active and passive immune responses
CAR-T cells
Epitope vaccine
Memory cells
Supramolecular peptide hydrogel

Publisher's Copyright Statement

This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Supramolecular peptide hydrogel epitope vaccine functionalized with CAR-T cells for the treatment of solid tumors",

abstract = "Chimeric antigen receptor T-cell (CAR-T) therapy, which benefits from the perfect combination of gene editing techniques and antibody engineering, has shown outstanding clinical efficacy in hematological malignancies. Solid tumors present the next challenge due to their extremely complicated microenvironment and structural characteristics. Targeting efficiency and persistence are currently bottleneck issues in the clinical treatment of CAR-T. Beyond drugs and cytokines, biomaterials can modulate the immune response, assisting adoptive CAR-T cells in exerting their function. In this study, a supramolecular peptide hydrogel epitope vaccine was designed to serve as both a preparation medium and a reservoir for CAR-T cells. The self-assembling peptide formed a nanofiber scaffold through non-covalent interactions of amphiphilic amino acids and ion stabilizers. Firstly, the complementary peptide conjugated vaccine epitopes and CAR-T target sites were derived from different extracellular domains of the HER2 protein, and the combination treatment improved tumor antigen spreading and targeting efficiency. The epitope hydrogel promoted CAR-T cell proliferation, cytotoxic activity, and lymphocyte subpopulation transformation. Furthermore, the supramolecular peptide epitope vaccine encapsulated CAR-T (SPEV-CAR-T) induced endogenous humoral and cellular immune responses through a sustained release of the hydrogel and CAR-T cells, demonstrating superior anti-tumor effects in an in vivo mouse model. Most importantly, SPEV-CAR-T induced central memory cells in systemic immune tissues, addressing the poor persistence of single CAR-T therapy. The integration and complementation of active and passive immune responses in this all-in-one hydrogel epitope vaccine and CAR-T system facilitated a sequential succession of endogenous and exogenous immune responses, promoting persistent and specific tumor attack. SPEV-CAR-T showed superior therapeutic effects in solid tumors. {\textcopyright} 2025 The Authors.",

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author = "Pengxiang Yang and Xiaomin Yao and Xue Tian and Yuehan Wang and Leilei Gong and Yumin Yang and Jing Jie",

year = "2025",

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AU - Yang, Pengxiang

AU - Yao, Xiaomin

AU - Tian, Xue

AU - Wang, Yuehan

AU - Gong, Leilei

AU - Yang, Yumin

AU - Jie, Jing

PY - 2025/4

Y1 - 2025/4

N2 - Chimeric antigen receptor T-cell (CAR-T) therapy, which benefits from the perfect combination of gene editing techniques and antibody engineering, has shown outstanding clinical efficacy in hematological malignancies. Solid tumors present the next challenge due to their extremely complicated microenvironment and structural characteristics. Targeting efficiency and persistence are currently bottleneck issues in the clinical treatment of CAR-T. Beyond drugs and cytokines, biomaterials can modulate the immune response, assisting adoptive CAR-T cells in exerting their function. In this study, a supramolecular peptide hydrogel epitope vaccine was designed to serve as both a preparation medium and a reservoir for CAR-T cells. The self-assembling peptide formed a nanofiber scaffold through non-covalent interactions of amphiphilic amino acids and ion stabilizers. Firstly, the complementary peptide conjugated vaccine epitopes and CAR-T target sites were derived from different extracellular domains of the HER2 protein, and the combination treatment improved tumor antigen spreading and targeting efficiency. The epitope hydrogel promoted CAR-T cell proliferation, cytotoxic activity, and lymphocyte subpopulation transformation. Furthermore, the supramolecular peptide epitope vaccine encapsulated CAR-T (SPEV-CAR-T) induced endogenous humoral and cellular immune responses through a sustained release of the hydrogel and CAR-T cells, demonstrating superior anti-tumor effects in an in vivo mouse model. Most importantly, SPEV-CAR-T induced central memory cells in systemic immune tissues, addressing the poor persistence of single CAR-T therapy. The integration and complementation of active and passive immune responses in this all-in-one hydrogel epitope vaccine and CAR-T system facilitated a sequential succession of endogenous and exogenous immune responses, promoting persistent and specific tumor attack. SPEV-CAR-T showed superior therapeutic effects in solid tumors. © 2025 The Authors.

AB - Chimeric antigen receptor T-cell (CAR-T) therapy, which benefits from the perfect combination of gene editing techniques and antibody engineering, has shown outstanding clinical efficacy in hematological malignancies. Solid tumors present the next challenge due to their extremely complicated microenvironment and structural characteristics. Targeting efficiency and persistence are currently bottleneck issues in the clinical treatment of CAR-T. Beyond drugs and cytokines, biomaterials can modulate the immune response, assisting adoptive CAR-T cells in exerting their function. In this study, a supramolecular peptide hydrogel epitope vaccine was designed to serve as both a preparation medium and a reservoir for CAR-T cells. The self-assembling peptide formed a nanofiber scaffold through non-covalent interactions of amphiphilic amino acids and ion stabilizers. Firstly, the complementary peptide conjugated vaccine epitopes and CAR-T target sites were derived from different extracellular domains of the HER2 protein, and the combination treatment improved tumor antigen spreading and targeting efficiency. The epitope hydrogel promoted CAR-T cell proliferation, cytotoxic activity, and lymphocyte subpopulation transformation. Furthermore, the supramolecular peptide epitope vaccine encapsulated CAR-T (SPEV-CAR-T) induced endogenous humoral and cellular immune responses through a sustained release of the hydrogel and CAR-T cells, demonstrating superior anti-tumor effects in an in vivo mouse model. Most importantly, SPEV-CAR-T induced central memory cells in systemic immune tissues, addressing the poor persistence of single CAR-T therapy. The integration and complementation of active and passive immune responses in this all-in-one hydrogel epitope vaccine and CAR-T system facilitated a sequential succession of endogenous and exogenous immune responses, promoting persistent and specific tumor attack. SPEV-CAR-T showed superior therapeutic effects in solid tumors. © 2025 The Authors.

KW - Active and passive immune responses

KW - CAR-T cells

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KW - Memory cells

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DO - 10.1016/j.mtbio.2025.101517

M3 - RGC 21 - Publication in refereed journal

C2 - 39925713

SN - 2590-0064

VL - 31

JO - Materials Today Bio

JF - Materials Today Bio

M1 - 101517

ER -

Supramolecular peptide hydrogel epitope vaccine functionalized with CAR-T cells for the treatment of solid tumors

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

UN SDGs

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