Immunosuppressive strategies in lung transplantation

Chung, Peter; Dilling, Daniel F.

doi:10.21037/atm.2019.12.117

Cited by 37 publications

(31 citation statements)

References 103 publications

(101 reference statements)

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“…In this paper, we decided to load inside HA-modified PEGylated liposomes everolimus, an immunemodulator already used for CLAD affected patients, but that induces many side effects [ 15 ]. Our analysis demonstrated that PEG-LIP-HA400kDa were rather monodisperse although the polydispersity index was higher than other types of liposomes described in the literature by Iwase et al These authors reported lower PdI values around 0.18 for PEGylated liposomes containing everolimus having similar composition prepared with ethanol injection [ 26 ]; this difference is due to the sonication process performed by the authors after liposome formation.…”

Section: Discussionmentioning

confidence: 99%

“…Although everolimus is very efficient, its important side effects hamper its use in chronic disorders [ 14 ]. For instance, in lung transplanted patients, everolimus administration is associated with severe dyslipidemia, decreased wound healing, bone marrow toxicity, and increased risk of lung toxicity [ 15 ], often requiring discontinuation of the therapy.…”

Section: Introductionmentioning

confidence: 99%

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Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Pandolfi

Marengo

Japiassu

et al. 2021

IJMS

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Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Pandolfi

Marengo

Japiassu

et al. 2021

IJMS

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“…Almost 70,000 lung transplant cases have been reported worldwide between 1992 and 2018 [ 2 ]. Although a median survival has been improved from 4.7 to 6.7 years over the last decade [ 3 ], long-term survival remained the lowest compared to other solid organ transplants [ 4 ]. The long-term survival rate is limited by acute and chronic rejection, infectious complications, drug toxicities, and malignancies [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Maintenance immunosuppression is currently used to prevent acute and chronic rejection. The current drug regimen for lung transplantation consists of a combination of three orally administrated drugs, including a calcineurin inhibitor (e.g., cyclosporin or tacrolimus), anti-metabolite (e.g., mycophenolate or azathioprine), and corticosteroids [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects

et al. 2021

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Due to the low and erratic bioavailability of oral tacrolimus (TAC), the long-term survival rate following lung transplantation remained low compared to other solid organs. TAC was reformulated and developed as inhaled formulations by thin film freezing (TFF). Previous studies reported that inhaled TAC combined with 50% w/w lactose (LAC) was safe and effective for the treatment of lung transplant rejection in rodent models. In this study, we aimed to investigate the safety and tolerability of TFF TAC-LAC in human subjects. The formulation can be delivered to the lung as colloidal dispersions after reconstitution and as a dry powder. Healthy subjects inhaled TAC-LAC colloidal dispersions at 3 mg TAC/dose via a vibrating mesh nebulizer in the first stage of this study and TAC-LAC dry powder at 3 mg TAC/dose via a single dose dry powder inhaler in the second stage. Our results demonstrated that oral inhalation of TAC-LAC colloidal dispersions and dry powder exhibited low systemic absorption. Additionally, they were well-tolerated with no changes in CBC, liver, kidney, and lung functions. Only mild adverse side effects (e.g., cough, throat irritation, distaste) were observed. In summary, pulmonary delivery of TFF TAC-LAC would be a safe and promising therapy for lung transplant recipients.

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“…The traditional rationale behind induction is to delay initiation of maintenance immunosuppression, reduce its cumulative dose, and decrease acute cellular rejection (ACR) 11,12 . Induction immunosuppression can decrease the incidence of acute rejection, reduce or delay BOS onset and improve graft and patient survival 13–16 . Induction immunosuppression using rATG in deceased donor kidney transplant recipients is associated with a lower incidence of de novo DSA, AMR, and increased graft survival 17–20 .…”

Section: Introductionmentioning

confidence: 99%

Antithymocyte globulin is associated with a lower incidence of de novo donor‐specific antibody detection in lung transplant recipients: A single‐center experience

Narula

Khouzam

Álvarez

et al. 2021

Immunity Inflam & Disease

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Purpose Induction immunosuppression has improved the long‐term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor‐specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR). Methods Sixty‐seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR‐received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA. Results De novo HLA DSA were detected in 22/67 (32.8%) LTR within 1‐year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant. Conclusion Induction immunosuppression utilizing a modified regimen of single‐dose rATG is associated with a significant reduction in de novo DSA production in LTR.

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Immunosuppressive strategies in lung transplantation

Cited by 37 publications

References 103 publications

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects

Antithymocyte globulin is associated with a lower incidence of de novo donor‐specific antibody detection in lung transplant recipients: A single‐center experience

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