PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A correlation between in vitro immunological and in vivo clinical studies

Yaelle Bavli; Bing Mae Chen; Steve R. Roffler; Marina A. Dobrovolskaia; Eldad Elnekave; Shifra Ash; Yechezkel Barenholz; Keren Turjeman

doi:10.3390/molecules25030558

PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A correlation between in vitro immunological and in vivo clinical studies

Yaelle Bavli, Bing Mae Chen, Steve R. Roffler, Marina A. Dobrovolskaia, Eldad Elnekave^*, Shifra Ash, Yechezkel Barenholz, Keren Turjeman

^*Corresponding author for this work

Department of Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase.

Original language	English
Article number	558
Journal	Molecules
Volume	25
Issue number	3
DOIs	https://doi.org/10.3390/molecules25030558
State	Published - 28 Jan 2020

Bibliographical note

Funding Information:
This work was supported by 3 sources: 1) A grant by the Innovative Materials and Analytical Technology Exploration (i-MATE) Program of Academia Sinica, Taiwan (AS-iMATE-107-97) to SR and YB. 2) The Barenholz fund which was established by the Hebrew University from part of the royalties of Barenholz inventions (especially Doxil?) dedicated to support Barenholz Lab research activities. 3) The study was supported in part (M.A.D.) by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We are grateful to Barry Neun and Edward Cedrone for the excellent technical support and to Moria Barlev-Gross for her help in the preparation on NSSL-MPS formulations.

Funding Information:
Funding: This work was supported by 3 sources: 1) A grant by the Innovative Materials and Analytical Technology Exploration (i‐MATE) Program of Academia Sinica, Taiwan (AS‐iMATE‐107‐ 97) to SR and YB. 2) The Barenholz fund which was established by the Hebrew University from part of the royalties of Barenholz inventions (especially Doxil®) dedicated to support Barenholz Lab research activities. 3) The study was supported in part (M.A.D.) by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Publisher Copyright:
© 2020 by the authors.

Keywords

Anti-PEG antibodies
Complement activation
Hypersensitive reactions
IgG4 related disease
Liposomal steroids
PEGylated nanodrugs

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title = "PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A correlation between in vitro immunological and in vivo clinical studies",

abstract = "PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase.",

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author = "Yaelle Bavli and Chen, {Bing Mae} and Roffler, {Steve R.} and Dobrovolskaia, {Marina A.} and Eldad Elnekave and Shifra Ash and Yechezkel Barenholz and Keren Turjeman",

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PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A correlation between in vitro immunological and in vivo clinical studies

Abstract

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Keywords

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