Journal Article

Optogenetic control of chemokine receptor signal and T-cell migration

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

2014

Overview

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 PA-CXCR4 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Amino Acid Sequence / Animals / Biological Sciences / Cell Adhesion - radiation effects / Cell membranes / Cell Movement - radiation effects / Cell Polarity - immunology / Cell Polarity - radiation effects / Chemokine receptors / Chemokines / CXCR4 receptor / cytotoxicity / Dimerization / Homing / immunity / Immunotherapy / Leukocytes / Light / Melanoma / Mice / Molecular Sequence Data / Neoplasms - immunology / Neoplasms - therapy / Optical control / Optical fibers / Optogenetics / patients / phototaxis / Protein Engineering / Receptors / Receptors, CXCR4 - chemistry / Receptors, CXCR4 - metabolism / Signal Transduction - radiation effects / T cell receptors / T lymphocytes / T-Lymphocytes - cytology / T-Lymphocytes - immunology / tissues / Tumors