Conformal Nanoencapsulation of Allogeneic T Cells Mitigates Graft-versus-Host Disease and Retains Graft-versus-Leukemia Activity

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 (similar to 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.