In vivo tracking of bioorthogonally labeled T-cells for predicting therapeutic efficacy of adoptive T-cell therapy
- Authors
- Kim, W.; Yoon, H.Y.; Lim, S.; Stayton, P.S.; Kim, I.-S.; Kim, K.; Kwon, I.C.
- Issue Date
- 10-1월-2021
- Publisher
- Elsevier B.V.
- Keywords
- Adoptive T-cell therapy; Bioorthogonal click chemistry; in vivo imaging; T-cell tracking
- Citation
- Journal of Controlled Release, v.329, pp.223 - 236
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Controlled Release
- Volume
- 329
- Start Page
- 223
- End Page
- 236
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/49391
- DOI
- 10.1016/j.jconrel.2020.12.002
- ISSN
- 0168-3659
- Abstract
- Non-invasive tracking of T-cells may help to predict the patient responsiveness and therapeutic outcome. Herein, we developed bioorthogonal T-cell labeling and tracking strategy using bioorthogonal click chemistry. First, ovalbumin (OVA) antigen-specific cytotoxic T-cells (CTLs) were incubated with N-azidoacetyl-D-mannosamine-tetraacylated (Ac4ManNAz) for incorporating azide ([sbnd]N3) groups on the surface of CTLs via metabolic glycoengineering. Subsequently, azide groups on the CTLs were chemically labeled with near infrared fluorescence (NIRF) dye, Cy5.5, conjugated dibenzylcyclooctyne (DBCO-Cy5.5) via bioorthogonal click chemistry, resulting in Cy5.5-labeled CTLs (Cy5.5-CTLs). The labeling efficiency of Cy5.5-CTLs could be readily controlled by changing concentrations of Ac4ManNAz and DBCO-Cy5.5 in cultured cells. Importantly, Cy5.5-CTLs presented the strong NIRF signals in vitro and they showed no significant changes in the functional properties, such as cell viability, proliferation, and antigen-specific cytolytic activity. In ovalbumin (OVA)-expressing E.G-7 tumor-bearing immune-deficient mice, intravenously injected Cy5.5-CTLs were clearly observed at targeted solid tumors via non-invasive NIRF imaging. Moreover, tumor growth inhibition of E.G-7 tumors was closely correlated with the intensity of NIRF signals from Cy5.5-CTLs at tumors after 2–3 days post-injection. The Cy5.5-CTLs showed different therapeutic responses in E.G-7 tumor-bearing immune-competent mice, in which they were divided by their tumor growth efficacy as ‘high therapeutic response (TR (+))’ and ‘low therapeutic response (TR (-))’. These different therapeutic responses of Cy5.5-CTLs were highly correlated with the NIRF signals of Cy5.5-CTLs at targeted tumor tissues in the early stage. Therefore, non-invasive tracking of T-cells can be able to predict and elicit therapeutic responses in the adoptive T-cell therapy. © 2020
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