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.

Biological responses of T cells encapsulated with polyelectrolyte-coated gold nanorods and their cellular activities in a co-culture system

“…2a). Our results are consistent with the previous work published by Zhao et al (2016) that used chitosan and alginate to conduct a conformal encapsulation of T cells.…”

“…The change in zeta potential value clearly indicates that Jurkat T cells were encapsulated in PAH or PSS-GNR/PAH. Our results were similar to previous works that investigated the zeta potential values of mammalian cells coated with different polymers (Zhao et al 2016;Pandey et al 2013;Bondar et al 2012). As can be seen, PAH@Jurkat cells had a weak negative value of zeta potential (-9.7 ± 0.2 mV) and the zeta potential value altered to have a further negative value after encapsulating Jurkat T cells with PSSGNRs.…”

“…And, available results of this study strongly suggest that PSS-GNRs could modify the surface of PAH@Jurkat cells resulting in changing of zeta potential values. The binding of a weak negative charge on the cell surface to negatively charged polymers was also reported (Zhao et al 2016). In the case of PSS/PAH@Jurkat cells, the zeta potential was more negative (-21.1 ± 0.4) than that of PSS-GNR/PAH@Jurkat cells (-11.3 ± 0.4).…”

“…Human T lymphocytes play an important role in the immune system and have been used in immunotherapy (Juan et al 2009;Zhao et al 2016). Unfortunately, T lymphocytes from a donor can be activated or interact with cells in the immune system of a recipient, leading to adverse effects (Roncarolo and Battaglia 2007).…”

Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction

“…For example, temporary systemic immunosuppression for up to 6 days was shown to mitigate immune rejection to bare pluripotent stem cells and their derivatives in the long term111213. Our recent study shows that the impact of temporary immunoisolation for 3 days could last over 80 days in a T cell-based therapy of leukaemia46.…”