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
Affiliations
Yaelle Bavli
Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 9112102, Israel
Bing-Mae Chen
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
Steve R. Roffler
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
Marina A. Dobrovolskaia
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA
Eldad Elnekave
Davidoff Cancer Institute, Rabin Medical Center, Petach Tikva 4941492, Israel
Shifra Ash
Rina Zaizov Pediatric Hematology Oncology Division, Schneider Children’s Medical Center of Israel, Petach Tiqva, Tel Aviv University, Tel Aviv, Israel 4920235, Israel
Yechezkel Barenholz
Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 9112102, Israel
Keren Turjeman
Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 9112102, Israel
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.
