Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies

Enbo Zhu; Jiaji Yu; Yan-Ruide Li; Feiyang Ma; Yu-Chen Wang; Yang Liu; Miao Li; Yu Jeong Kim; Yichen Zhu; Zoe Hahn; Yang Zhou; James Brown; Yuchong Zhang; Matteo Pelegrini; Tzung Hsiai; Lili Yang; Yu Huang

doi:10.1038/s41565-024-01781-4

Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies

Nat Nanotechnol. 2024 Sep 23. doi: 10.1038/s41565-024-01781-4. Online ahead of print.

Authors

Enbo Zhu^#^{1

2

3

4}, Jiaji Yu^#², Yan-Ruide Li², Feiyang Ma⁵, Yu-Chen Wang², Yang Liu¹, Miao Li², Yu Jeong Kim², Yichen Zhu², Zoe Hahn², Yang Zhou², James Brown², Yuchong Zhang², Matteo Pelegrini⁵, Tzung Hsiai^{3

4}, Lili Yang^{6

7

8

9}, Yu Huang^{10

11

12}

Affiliations

¹ Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].
⁷ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].
⁸ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].
⁹ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].
¹⁰ Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].
¹¹ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].
¹² California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA. [email protected].

^# Contributed equally.

PMID: 39313679
DOI: 10.1038/s41565-024-01781-4

Abstract

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP^3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP^3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP^3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation.

Abstract

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