Nanoallergen platform for detection of platin drug allergies

[...]a lipid tail was added by addition of a palmitic acid tail to form the peptide-lipid. Nanoallergens synthesized with 5% oxaliplatin-lipid were termed nanooxpt, whereas nanoallergens synthesized with 5% carboplatin-lipid were termed nanocpt.Particle characterization Liposomes were measured for s...

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Veröffentlicht in:Journal of allergy and clinical immunology 2019-05, Vol.143 (5), p.1957-1960.e12
Hauptverfasser: Deak, Peter E., Kim, Baksun, Adnan, Ather, Labella, Marina, De las Vecillas, Leticia, Castells, Mariana, Bilgicer, Basar
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Sprache:eng
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Zusammenfassung:[...]a lipid tail was added by addition of a palmitic acid tail to form the peptide-lipid. Nanoallergens synthesized with 5% oxaliplatin-lipid were termed nanooxpt, whereas nanoallergens synthesized with 5% carboplatin-lipid were termed nanocpt.Particle characterization Liposomes were measured for size by using dynamic light scattering analysis with the 90Plus nanoparticle size analyzer (Brookhaven Instruments, Holtsvile, NY) at 658 nm of light observed and a fixed angle of 90° at 20°C. Liposome samples were diluted with a 0.22 μmol/L filter-sterilized PBS to a 1.25 nmol/L liposome concentration immediately after extrusion, placed in a 50-μL quartz cuvette, and particle sized.Nanoallergen stability study To determine the stability of platin-presenting nanoallergens, we synthesized 10 nmol/L solutions of either nanooxpt or nanocpt and then either kept them at 4°C or flash froze them in liquid nitrogen and stored them at −80°C for various time points. [...]cells were removed from the plate and split 1:3 into fresh media.Human sera and preparation Human sera from oncologic patients with a previous severe systemic immediate hypersensitivity reaction to carboplatin or oxaliplatin and/or a positive skin test (prick and intradermal) response undergoing desensitization were obtained from Brigham and Women's Hospital.E6-E8 All patients included in the study provided written informed consent and were recruited after approved application from the Biomedical Research-Dana-Farber/Harvard Cancer Center-BIDMC/BCH/BWH/DFCI/MGH/Partners Network Affiliates (DFCI protocol no. 13-288). Stored at 4°C Stored at −80°C Diameter (nm) SE PD SE Diameter (nm) SE PD SE Nanooxpt Day 0 368.74 6.21 0.18 0.053 391.67 3.3 0.176 0.059 Day 1 367.25 2.91 0.187 0.012 387.25 1.72 0.148 0.022 Day 2 372.94 1.69 0.159 0.02 395.74 1.48 0.183 0.025 Day 7 414.17 1.79 0.23 0.018 385.92 1.74 0.166 0.017 Nanocpt Day 0 384.76 2.89 0.188 0.036 450.51 3.5 0.145 0.023 Day 1 398.13 5.99 0.196 0.015 443.81 3.54 0.161 0.008 Day 2 399.7 3.5 0.133 0.021 439.99 2.43 0.181 0.021 Day 7 399.37 3.78 0.135 0.028 441.07 2.21 0.188 0.023 Table E1 Particle size stability Patient Sex Age (y) Drug Type of cancer No. of lifetime infusions before reaction Reaction grade Symptoms during reaction Skin tests Atopy Tryptase (ng/mL) 2 F 75 Carboplatin Ovarian >10 1 Flushing and itching Positive at first ID (1 mg/mL) Rhinitis and asthma, drug allergy (flushing with levofloxacin) 18.2 (during first RDD) 5.7 (baseline) 3 F 68 Carbop
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2019.01.010