NDLI: In vivo Targeting of Adoptively Transferred T-cells with Antibody- and Cytokine-Conjugated Liposomes

Content Provider	PubMed Central
Author	Zheng, Yiran Stephan, Matthias Gai, S. Annie Abraham, Wuhbet Shearer, Adrianne Irvine, Darrell J.
Abstract	In adoptive cell therapy (ACT), autologous tumor-specific T-cells isolated from cancer patients are activated and expanded ex vivo, then infused back into the individual to eliminate metastatic tumors. A major limitation of this promising approach is the rapid loss of ACT T-cell effector function in vivo due to the highly immunosuppressive environment in tumors. Protection of T-cells from immunosuppressive signals can be achieved by systemic administration of supporting adjuvant drugs such as interleukins, chemotherapy, and other immunomodulators, but these adjuvant treatments are often accompanied by serious toxicities and may still fail to optimally stimulate lymphocytes in all tumor and lymphoid compartments. Here we propose a novel strategy to repeatedly stimulate or track ACT T-cells, using cytokines or ACT-cell-specific antibodies as ligands to target PEGylated liposomes to transferred T-cells in vivo. Using F(ab′)2 fragments against a unique cell surface antigen on ACT cells (Thy1.1) or an engineered interleukin-2 (IL-2) molecule on an Fc framework as targeting ligands, we demonstrate that >95% of ACT cells can be conjugated with liposomes following a single injection in vivo. Further, we show that IL-2-conjugated liposomes both target ACT cells and are capable of inducing repeated waves of ACT T-cell proliferation in tumor-bearing mice. These results demonstrate the feasibility of repeated functional targeting of T-cells in vivo, which will enable delivery of imaging contrast agents, immunomodulators, or chemotherapy agents in adoptive cell therapy regimens.
Related Links	http://dx.doi.org/10.1016/j.jconrel.2013.05.037
Ending Page	435
Page Count	10
Starting Page	426
File Format	PDF
ISSN	01683659
e-ISSN	18734995
Journal	Journal of controlled release : official journal of the Controlled Release Society
Issue Number	2
Volume Number	172
Language	English
Publisher Date	2013-12-01
Access Restriction	Open
Subject Keyword	Pharmaceutical Science Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science

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