title: Conformal Nanoencapsulation of Allogeneic T Cells Mitigates Graft-versus-Host Disease and Retains Graft-versus-Leukemia Activity.
abstract: 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 (∼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.
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University , Hefei 230032, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Han
authors.affiliation: Suzhou Institute of Blood and Marrow Transplantation, Soochow University , Suzhou 215000, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chu
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: Xilin
authors.initials: X
authors.lastname: Chen
authors.forename: Youwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Norm
authors.initials: N
authors.lastname: Tun
authors.forename: Lanchun
authors.initials: L
authors.lastname: Lu
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
authors.forename: Martha
authors.initials: M
authors.lastname: Yearsley
authors.forename: Steven
authors.initials: S
authors.lastname: Devine
authors.forename: Xiaoming
authors.initials: X
authors.lastname: He
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D006086:Graft vs Host Disease; D020544:Graft vs Leukemia Effect; D007938:Leukemia; D051379:Mice; D053761:Nanocomposites; D013601:T-Lymphocytes; D014184:Transplantation, Homologous
keywords: T cells; alginate; chitosan; graft-versus-host disease; graft-versus-leukemia; immunoisolation; nanomaterials