PMID- 27224853 OWN - NLM STAT- MEDLINE DCOM- 20180730 LR - 20181202 IS - 1936-086X (Electronic) IS - 1936-0851 (Print) IS - 1936-0851 (Linking) VI - 10 IP - 6 DP - 2016 Jun 28 TI - Conformal Nanoencapsulation of Allogeneic T Cells Mitigates Graft-versus-Host Disease and Retains Graft-versus-Leukemia Activity. PG - 6189-200 LID - 10.1021/acsnano.6b02206 [doi] AB - Allogeneic transplantation of hematopoietic stem cells (HSC) in combination with T cells has a curative potential for hematopoietic malignancies through graft-versus-leukemia (GVL) effects, but is often compromised by the notorious side effect of graft-versus-host disease (GVHD) resulting from alloreactivity of the donor T cells. Here, we tested if temporary immunoisolation achieved by conformally encapsulating the donor T cells within a biocompatible and biodegradable porous film ( approximately 450 nm in thickness) of chitosan and alginate could attenuate GVHD without compromising GVL. The nanoencapsulation was found not to affect the phenotype of T cells in vitro in terms of size, viability, proliferation, cytokine secretion, and cytotoxicity against tumor cells. Moreover, the porous nature of the nanoscale film allowed the encapsulated T cells to communicate with their environment, as evidenced by their intact capability of binding to antibodies. Lethally irradiated mice transplanted with bone marrow cells (BMCs) and the conformally encapsulated allogeneic T cells exhibited significantly improved survival and reduced GVHD together with minimal liver damage and enhanced engraftment of donor BMCs, compared to the transplantation of BMCs and non-encapsulated allogeneic T cells. Moreover, the conformal nanoencapsulation did not compromise the GVL effect of the donor T cells. These data show that conformal nanoencapsulation of T cells within biocompatible and biodegradable nanoscale porous materials is a potentially safe and effective approach to improve allogeneic HSC transplantation for treating hematological malignancies and possibly other diseases. FAU - Zhao, Shuting AU - Zhao S FAU - Zhang, Lingling AU - Zhang L AD - Institute of Clinical Pharmacology, Anhui Medical University , Hefei 230032, China. FAU - Han, Jianfeng AU - Han J FAU - Chu, Jianhong AU - Chu J AD - Suzhou Institute of Blood and Marrow Transplantation, Soochow University , Suzhou 215000, China. FAU - Wang, Hai AU - Wang H FAU - Chen, Xilin AU - Chen X FAU - Wang, Youwei AU - Wang Y FAU - Tun, Norm AU - Tun N FAU - Lu, Lanchun AU - Lu L FAU - Bai, Xue-Feng AU - Bai XF FAU - Yearsley, Martha AU - Yearsley M FAU - Devine, Steven AU - Devine S FAU - He, Xiaoming AU - He X FAU - Yu, Jianhua AU - Yu J LA - eng GR - R01 AI123661/AI/NIAID NIH HHS/United States GR - R01 CA068458/CA/NCI NIH HHS/United States GR - R01 CA155521/CA/NCI NIH HHS/United States GR - R01 CA185301/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160531 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 SB - IM MH - Animals MH - *Graft vs Host Disease MH - *Graft vs Leukemia Effect MH - Leukemia MH - Mice MH - *Nanocomposites MH - *T-Lymphocytes MH - Transplantation, Homologous PMC - PMC5514314 MID - NIHMS875671 OTO - NOTNLM OT - T cells OT - alginate OT - chitosan OT - graft-versus-host disease OT - graft-versus-leukemia OT - immunoisolation OT - nanomaterials COIS- Notes The authors declare the following competing financial interest(s): SZ and XH disclosed the technology of conformal nanoencapsulation of cells and tissues to the Technology and Commercialization Office at The Ohio State University, Columbus, Ohio, USA. EDAT- 2016/05/26 06:00 MHDA- 2018/07/31 06:00 PMCR- 2017/07/18 CRDT- 2016/05/26 06:00 PHST- 2016/05/26 06:00 [entrez] PHST- 2016/05/26 06:00 [pubmed] PHST- 2018/07/31 06:00 [medline] PHST- 2017/07/18 00:00 [pmc-release] AID - 10.1021/acsnano.6b02206 [doi] PST - ppublish SO - ACS Nano. 2016 Jun 28;10(6):6189-200. doi: 10.1021/acsnano.6b02206. Epub 2016 May 31.