Chapter 35 : Immunotherapy

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Immunotherapeutic strategies for invasive aspergillosis should be understood in the context of host defense deficits in high-risk patients and immunopathology of fungal disease. This chapter discusses the following strategies for immunotherapy for invasive aspergillosis: (i) augmentation of neutrophil number; (ii) pathogen recognition receptor (PRR) ligands; (iii) cytokine administration and depletion; and (iv) vaccination. Price et al. conducted a phase I / II study of granulocyte transfusions derived from unrelated, non- HLA-matched, community donors following G-CSF and dexamethasone mobilization. Eight of 11 patients with bacterial infections or candidemia survived, but all 8 patients with invasive mold infection died. This study showed the safety and feasibility of using community donors for granulocytapheresis donations. The Transfusion Medicine and Hemostasis Network of the National Heart, Lung and Blood Institute is in the planning stages of a randomized study of adjunctive granulocyte transfusions in neutropenic patients with severe bacterial and fungal infections. This study is expected to definitively evaluate the benefits and risks of adjunctive granulocyte transfusions. There are several potential cytokines and chemokines that can be exploited as immunotherapy for invasive aspergillosis. Adoptive transfer of Th1-committed CD4T cells conferred protection to neutropenic mice, establishing a proof of principle regarding cellular immunity as a target for immune augmentation in invasive aspergillosis. This study also showed that the dichotomy in which the host defense against extracellular pathogens is humoral while the defense against intracellular pathogens is cellular is overly simplistic. Antifungal agents have immunomodulatory effects that may be clinically relevant and exploitable for immunotherapeutic strategies.

Citation: Segal B, Romani L. 2009. Immunotherapy, p 467-478. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch35
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Model of contribution of T cells to host defense and inflammation against .

Citation: Segal B, Romani L. 2009. Immunotherapy, p 467-478. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch35
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Table 1.

Patients at risk for invasive aspergillosis

Citation: Segal B, Romani L. 2009. Immunotherapy, p 467-478. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch35
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Table 2.

Summary of immune augmentation strategies against aspergillosis

Citation: Segal B, Romani L. 2009. Immunotherapy, p 467-478. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch35

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