Immunotherapy Against Invasive Fungal Diseases in Stem Cell Transplant Recipients

Abstract

Despite the availability of new antifungal compounds, morbidity and mortality of invasive fungal disease in allogeneic hematopoietic stem cell recipients are still unacceptably high. Over the past decade, one could witness an exciting improvement of the understanding of the molecular pathogenesis and of the complexity of host antifungal immune responses. This, in turn, provides critical information to augment host immunity against fungal pathogens. Strategies for enhancing the immune system include the administration of effector and regulatory cells (e.g., granulocytes, antigen-specific T cells, dendritic cells) as well as the administration of recombinant cytokines, interferons and growth factors (e.g., interferon-γ, keratinocyte growth factor, granulocyte- and granulocyte-macrophage colony stimulating factor). One has to recognize at the same time, however, that data of in vitro assays and animal models cannot necessarily be transferred into the clinical setting. In addition, meaningful clinical trials in allogeneic stem cell recipients suffering from invasive fungal disease require sufficiently large and homogenous cohorts of patients and can only be performed in international collaboration, but may ultimately improve the outcome of allogeneic transplant recipients with invasive fungal disease.

Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series

“…As such, it has been implicated as a treatment option in (invasive) fungal infections [20,21]. Moreover, limited evidence suggests that recombinant IFN-γ (rIFN-γ) has a beneficial effect on the outcome of fungal infections in patients with chronic granulomatous disease (CGD) [22], HIV [23-25], leukemia [26,27], and in patients receiving organ transplants [28].…”

LAB/NTAL Facilitates Fungal/PAMP-induced IL-12 and IFN-γ Production by Repressing β-Catenin Activation in Dendritic Cells

“…There is a high degree of mortality in these cases even with treatment, highlighting the need for a better understanding of the immune response involved in controlling fungal infections in order to develop improved treatments [2], [3]. Responses to fungal infections involve both innate and adaptive immunity [4].…”

Immunotherapy for viral and fungal infections

“…12 In addition, we and others have shown that also activated natural killer cells-which can be easily selected and enriched for-can mediate anti-aspergillus activity. [13][14][15] Data from our group have also demonstrated that isolated gamma-delta T cells can mediate anti-aspergillus activity. 11 Gamma-delta T lymphocytes can be highly enriched for under good manufacturing practice conditions using the Clinimacs device 16,17 and also easily be activated and expanded in vivo by stimulation with aminobisphosphonates.…”