Antiviral T-cell therapy

Abstract

Serious viral infections are a common cause of morbidity and mortality after allogeneic stem cell transplantation. They occur in the majority of allograft recipients and are fatal in 17-20%. These severe infections may be prolonged or recurrent and add substantially to the cost, both human and financial, of the procedure. Many features of allogeneic stem cell transplantation contribute to this high rate of viral disease. The cytotoxic and immunosuppressive drugs administered pretransplant to eliminate the host hematopoietic/immune system and any associated malignancy, the delay in recapitulating immune ontogeny post-transplant, the immunosuppressive drugs given to prevent graft versus host disease (GvHD), and the effects of GvHD itself, all serve to make stem cell transplant recipients vulnerable to disease from endogenous (latent) and exogenous (community) viruses, and to be incapable of controlling them as quickly and effectively as most normal individuals.

Keywords: T cells; immunotherapies; transplantation.

Figure 1

Frequency of virus‐specific T cells in peripheral blood. The frequency of circulating virus‐specific T cells directed against CMV (IE1 and pp65), EBV (LMP1, LMP2, EBNA1, EBNA3a, EBNA3b, EBNA3c, BZLF1), AdV (Hexon and Penton), Influenza (NP1 and MP1), HHV6 (U11, U14, and U90), BK virus (Large T and VP1), and RSV (N and F) was evaluated by IFNγ ELIspot. Results are presented as spot forming cells (SFC) per 5 × 10⁵ PBMCs ± SEM (n = 5).

Figure 2

Rapid section of virus‐specific T cells. Peptide‐HLA multimers (A) and cytokine‐secretion capture (B) have both been used clinically to select virus‐specific T cells for adoptive transfer. Multimer selection isolates T cells based on the ability of their TCR to bind to a complex of synthetic peptide‐loaded recombinant HLA molecules, while the cytokine capture approach selects T cells (both CD4⁺ and CD8⁺) based on their ability to secrete effector cytokines in response to viral antigen stimulation.