Enhanced delivery of T cells to tumor after chemotherapy using membrane-anchored, apoptosis-targeted peptide

Xiaofeng He, Napolean Bonaparte, Soyoun Kim, Bodhraj Acharya, Ji Young Lee, Lianhua Chi, Hyoung Joo Lee, Young Ki Paik, Pyong Gon Moon, Moon Chang Baek, Eun Kyu Lee, Jong Ho Kim, In San Kim, Byung Heon Lee

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9 Citations (Scopus)

Abstract

Chemotherapy-induced apoptosis of tumor cells enhances the antigen presentation and sensitizes tumor cells to T cell-mediated cytotoxicity. Here we harnessed the apoptosis of tumor cells as a homing signal for the delivery of T cells to tumor. Jurkat T cells were anchored with ApoPep-1, an apoptosis-targeted peptide ligand, using the biocompatible anchor for membrane (BAM), an oleyl acid derivative. The ApoPep-1-BAM conjugate was efficiently anchored to cell membrane, while little anchoring was obtained with ApoPep-1 alone. The retention period of the ApoPep-1-BAM conjugate on cell membrane was approximately 80 and 40 min in the absence and presence of serum, respectively. ApoPep-1 was resistant to degradation in serum until 2 h. The apoptosis-targeted T cells that were anchored with the ApoPep-1-BAM preferentially bound to apoptotic tumor cells over living cells. When intravenously injected into tumor-bearing mice, the number of apoptosis-targeted T cells and in vivo fluorescence signals by the homing of the cells to doxorubicin-treated tumor were higher than those of untargeted T cells. Accumulation of apoptosis-targeted T cells at other organs such as liver was not detected. These results suggest that the chemotherapy-induced apoptosis and subsequent enhancement of T cell delivery to tumor by the membrane anchoring of the apoptosis-targeted peptide could be a novel strategy for cancer immunotherapy.

Original languageEnglish
Pages (from-to)521-528
Number of pages8
JournalJournal of Controlled Release
Volume162
Issue number3
DOIs
Publication statusPublished - 2012 Sep 28

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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    He, X., Bonaparte, N., Kim, S., Acharya, B., Lee, J. Y., Chi, L., Lee, H. J., Paik, Y. K., Moon, P. G., Baek, M. C., Lee, E. K., Kim, J. H., Kim, I. S., & Lee, B. H. (2012). Enhanced delivery of T cells to tumor after chemotherapy using membrane-anchored, apoptosis-targeted peptide. Journal of Controlled Release, 162(3), 521-528. https://doi.org/10.1016/j.jconrel.2012.07.023