Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.

in Nature biomedical engineering by Zeyang Liu, Yan-Ruide Li, Youcheng Yang, Yu Zhu, Weihao Yuan, Tyler Hoffman, Yifan Wu, Enbo Zhu, Jana Zarubova, Jun Shen, Haochen Nan, Kun-Wei Yeh, Mohammad Mahdi Hasani-Sadrabadi, Yichen Zhu, Ying Fang, Xinyang Ge, Zhizhong Li, Jennifer Soto, Tzung Hsiai, Lili Yang, Song Li

TLDR

  • The study developed synthetic viscoelastic cells that mimic antigen-presenting cells, resulting in enhanced expansion of engineered T cells and improved immunotherapy outcomes.

Abstract

The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8T cells and to the suppression of the formation of regulatory T cells. Notably, activating and expanding chimaeric antigen receptor (CAR) T cells with SynVACs led to a CAR-transduction efficiency of approximately 90% and to substantial increases in T memory stem cells. The engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, persisted for longer periods and reduced tumour-recurrence risk. Our findings underscore the crucial roles of viscoelasticity in T-cell engineering and highlight the utility of SynVACs in cancer therapy.

Overview

  • The study aims to improve synthetic antigen-presenting cells (SynVACs) for the treatment of cancers by mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells.
  • The researchers developed a high-throughput microfluidic system to fabricate SynVACs and compared their effectiveness with rigid or elastic microspheres.
  • The primary objective of the study is to explore the potential of SynVACs in cancer therapy, particularly in the activation and expansion of engineered T cells.

Comparative Analysis & Findings

  • SynVACs led to substantial enhancements in the expansion of human CD8T cells and the suppression of regulatory T cells compared to rigid or elastic microspheres.
  • The activation and expansion of chimeric antigen receptor (CAR) T cells with SynVACs resulted in a CAR-transduction efficiency of approximately 90% and significant increases in T memory stem cells.
  • Engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, and persisted for longer periods.

Implications and Future Directions

  • The study highlights the crucial roles of viscoelasticity in T-cell engineering and underscores the potential of SynVACs in cancer therapy.
  • Future research directions may include optimizing the synthesis of SynVACs and exploring their potential in combination with other immunotherapies.
  • The findings of this study may pave the way for the development of more effective and durable CAR T cell therapies for the treatment of various cancers.
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