Immunotherapy for opportunistic infections: Current status and future perspectives

Abstract

The outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) has significantly improved during the last decades. However, opportunistic infections such as viral and mold infections are still a major obstacle for cure. Within this field, adoptive T cell therapy against pathogens is a promising treatment approach. Recently, the techniques to develop T cell products including pathogen-specific T cells have been sophisticated and are now available in accordance to good manufacturing practice (GMP). Here, we aim to summarize current knowledge about adoptive T cell therapy against viral and mold infections.

Robust Identification of Suitable T-Cell Subsets for Personalized CMV-Specific T-Cell Immunotherapy Using CD45RA and CD62L Microbeads

“…In immunocompromised transplant recipients, long-term control of viral infection and reactivation relies on the recovery and reconstitution of antiviral CD4 + and CD8 + T cells. Donor lymphocyte infusions (DLIs) and the transfer of enriched antiviral T cells have been proven effective in reconstituting the immune system and in preventing and controlling the reactivation of opportunistic infections following transplantation [1,20,21,22,23]. DLIs have a broad antiviral T-cell repertoire, but their application is limited because alloreactive naive T cells still present in these products have the potential to cause GvHD.…”

“…Current strategies include: (1) enrichment via an interferon-γ (IFN-γ) cytokine capture system (CCS) [12,13,14]; (2) reversible peptide-MHC (pMHC) multimers [15,16,17]; as well as (3) in vitro expansion from a small number of precursor cells in the presence of specific antigens and different cytokine combinations [18,19]. All of the above-mentioned strategies have achieved promising viral eradication results [20,21,22,23]. Nonetheless, the ability to generate these antiviral memory T-cell products is limited as they require knowledge of immunodominant viral epitopes and the availability of good manufacturing practice (GMP)-quality grade antigens for stimulation and enrichment [20].…”

Hyperglycemia as a possible risk factor for mold infections—the potential preventative role of intensified glucose control in allogeneic hematopoietic stem cell transplantation

“…9 Recent findings also suggest the importance of adaptive immunity such as Th1 cells, which was reviewed elsewhere. 10 The significantly increased risk of fungal infections in patients with chronic granulomatous disease, which is genetically associated with defective phagocyte function, supports the importance of phagocytes in the control of mold infections. [11][12][13] There are several causes of insufficient protection by neutrophils, as summarized in Table 1.…”

Recent Advances in the Treatment of Scedosporiosis and Fusariosis

“…While, until now, most immunotherapeutic approaches have aimed to augment the number of granulocytes through granulocyte transfusions, the infusion of growth factors (G-CSF, GM-CSF), the administration of cytokines such as IFN-γ, and most recently, the use of adoptive T cell therapy, which was initiated for the treatment of cancer, seems to be a promising approach for the treatment of patients suffering from drug-resistant IFI [ 119 ]. Even though there is growing evidence supporting the role of T cell adoptive therapy in antifungal immunity, the clinical development of fungus-specific T cells is in the early stages of development, and there is a paucity of data regarding adoptive T cell therapy using Scedosporium- or Fusarium- specific T cells [ 120 ].…”