Optogenetic control of chemokine receptor signal and T-cell migration

Yuexin Xu, Young Min Hyun, Kihong Lim, Hyunwook Lee, Ryan J. Cummings, Scott A. Gerber, Seyeon Bae, Thomas Yoonsang Cho, Edith M. Lord, Minsoo Kim

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Adoptive cell transfer of ex vivo-generated immune-promoting or tolerogenic T cells to either enhance immunity or promote tolerance in patients has been used with some success. However, effective trafficking of the transferred cells to the target tissue sites is the main barrier to achieving successful clinical outcomes. Here we developed a strategy for optically controlling T-cell trafficking using a photoactivatable (PA) chemokine receptor. Photoactivatable-chemokine C-X-C motif receptor 4 (PA-CXCR4) transmitted intracellular CXCR4 signals in response to 505-nm light. Localized activation of PACXCR4 induced T-cell polarization and directional migration (phototaxis) both in vitro and in vivo. Directing light onto the melanoma was sufficient to recruit PA-CXCR4-expressing tumor-targeting cytotoxic T cells and improved the efficacy of adoptive T-cell transfer immunotherapy, with a significant reduction in tumor growth in mice. These findings suggest that the use of photoactivatable chemokine receptors allows remotely controlled leukocyte trafficking with outstanding spatial resolution in tissues and may be feasible in other cell transfer therapies.

Original languageEnglish (US)
Pages (from-to)6371-6376
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number17
DOIs
StatePublished - Apr 29 2014

All Science Journal Classification (ASJC) codes

  • General

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