Cytokine conjugation to enhance T cell therapy

Yutong Liu, Kwasi Adu-Berchie, Joshua M. Brockman, Matthew Pezone, David K.Y. Zhang, Jingyi Zhou, Jason W. Pyrdol, Hua Wang, Kai W. Wucherpfennig, David J. Mooney

Research output: Contribution to journalArticlepeer-review


Adoptive T cell transfer (ACT) therapies suffer from a number of limitations (e.g., poor control of solid tumors), and while combining ACT with cytokine therapy can enhance effectiveness, this also results in significant side effects. Here, we describe a nanotechnology approach to improve the efficacy of ACT therapies by metabolically labeling T cells with unnatural sugar nanoparticles, allowing direct conjugation of antitumor cytokines onto the T cell surface during the manufacturing process. This allows local, concentrated activity of otherwise toxic cytokines. This approach increases T cell infiltration into solid tumors, activates the host immune system toward a Type 1 response, encourages antigen spreading, and improves control of aggressive solid tumors and achieves complete blood cancer regression with otherwise noncurative doses of CAR-T cells. Overall, this method provides an effective and easily integrated approach to the current ACT manufacturing process to increase efficacy in various settings.

Original languageEnglish (US)
Article numbere2213222120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 3 2023
Externally publishedYes


  • CAR-T
  • adoptive T cell transfer
  • metabolic labeling; anti-tumor cytokine
  • nanoparticle

ASJC Scopus subject areas

  • General


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