Ignite Creation Date:
2024-05-06 @ 8:11 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06285188
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-29
First Post:
2024-02-22
Brief Title:
Immunomonitoring of Mold Invasive Infections
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Immunomonitoring of Mold Invasive Infections
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMMUNOFIL
Brief Summary:
Mold invasive infections are associated with an important mortality despite optimization of the antifungal treatment In a few case reports immune checkpoints inhibitors initially developed for neoplastic diseases have shown a potential beneficial effect in such devastating infections by restoring an efficient immune response The investigators propose a longitudinal monitoring of the adaptative immune response notably immune checkpoint expression on T cells during mold invasive infections to help identify the patients who could benefit from the adjunction of immunotherapy and the optimal timing of such strategy
Detailed Description:
Invasive fungal diseases IFD still cause substantial morbidity and mortality New therapeutic approaches are therefore urgently needed notably for patients not responding to conventional antifungal treatment One strategy to prevent treatment failure is to improve the immune functions of immunocompromised hosts Indeed antifungals therapeutic efficacy is limited without the help of host immune reactivity Stevens et al 2000 As several studies have suggested that IFD are associated with an impaired Th1 host immune response various cytokines have been evaluated in experimental and human fungal infections In particular adjunction of recombinant IFNγ has been proposed as a treatment option in patients with poor prognosis IFD with partial success More recently it has been shown that when T cells are exposed to persistent antigens andor inflammatory signals due to inefficient control of persisting infections or in the context of tumors a deterioration of their functions is observed a state called exhaustion Molecular pathways involved in exhaustion have been partially deciphered highlighting the importance of molecules called immune checkpoint such as PD-1 or CTLA-4 Furthermore it was shown that blockade of these molecules can reverse this dysfunctional state Immune checkpoint inhibitors such as anti-PD1 antibodies have become major weapons in oncology In infectious diseases and more particularly IFDs data are much more limited In animal models of several IFD such as aspergillosis cryptococcosis and histoplasmosis repetitive administration of anti-PD-1 monoclonal antibodies significantly improved fungal clearance and survival of lethally infected animals In humans three case-reports including one published by our team have reported the efficacy of anti-PD-1 therapy combined with IFN-γ in the treatment of refractory IFDs Therefore by reversing T cell exhaustion immune checkpoint blockade represents a therapeutic perspective for IFD treatment
The use of immune checkpoint inhibitors may however entail severe notably autoimmune off-target adverse effects and should be carefully balanced and monitored The development of tools allowing identification of patients who could benefit from immunotherapy is of particular importance as well as assessment of the optimal timing of these innovative treatments As such a better understanding of the host immune response is one of the major approaches to developing new or improved antifungal strategies to control IFDs Longitudinal data regarding the evolution of exhaustion markers expression in T cells of patients treated for an IFD are lacking
The goal is to better characterize the adaptative immune response directed against molds notably immune checkpoint expression in order to identify the patients who could benefit from the adjunction of immunotherapy and the optimal timing of such strategy
For this purpose the investigators will include adult patients with mold IFD either at diagnosis or refractory to conventional therapy They will measure activation and exhaustion markers on circulating T cells and monocytes by flow cytometry at three timepoints enrollment day 14 and week 6 Moreover for patients with invasive aspergillosis or mucormycosis they will evaluate the capacity of specific T cells to produce Th1 Th2 and Th 17 cytokines and to proliferate after specific antigenic stimulation in the absence and in the presence of an anti-PD1 antibody in vitro 4 colors FLUOROSPOT at two timepoint enrollment and week 6 These data will provide a longitudinal assessment of the anti-fungal immune response They will be correlated with the underlying diseases of the patients the type of mold infection aspergillosis mucormycosis fusariosis or scedosporiosis the treatment received and the outcome These results should help to better identify patients who could benefit from adjunctive anti PD-1 treatment and the optimal timing for such treatment
The use of immune checkpoint inhibitors may however entail severe notably autoimmune off-target adverse effects and should be carefully balanced and monitored The development of tools allowing identification of patients who could benefit from immunotherapy is of particular importance as well as assessment of the optimal timing of these innovative treatments As such a better understanding of the host immune response is one of the major approaches to developing new or improved antifungal strategies to control IFDs Longitudinal data regarding the evolution of exhaustion markers expression in T cells of patients treated for an IFD are lacking
The goal is to better characterize the adaptative immune response directed against molds notably immune checkpoint expression in order to identify the patients who could benefit from the adjunction of immunotherapy and the optimal timing of such strategy
For this purpose the investigators will include adult patients with mold IFD either at diagnosis or refractory to conventional therapy They will measure activation and exhaustion markers on circulating T cells and monocytes by flow cytometry at three timepoints enrollment day 14 and week 6 Moreover for patients with invasive aspergillosis or mucormycosis they will evaluate the capacity of specific T cells to produce Th1 Th2 and Th 17 cytokines and to proliferate after specific antigenic stimulation in the absence and in the presence of an anti-PD1 antibody in vitro 4 colors FLUOROSPOT at two timepoint enrollment and week 6 These data will provide a longitudinal assessment of the anti-fungal immune response They will be correlated with the underlying diseases of the patients the type of mold infection aspergillosis mucormycosis fusariosis or scedosporiosis the treatment received and the outcome These results should help to better identify patients who could benefit from adjunctive anti PD-1 treatment and the optimal timing for such treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2023-A01398-37 | REGISTRY | ID-RCB | None |