Therapeutic use of avidin is not hampered by antiavidin antibodies in humans.
Hen egg white avidin is increasingly used in the clinic as part of multifactor treatments such as pretargeted radionuclide therapy of cancer or as an antidote of biotinylated drugs. Taking into account that naturally occurring human antiavidin antibodies (HAVA) are common in humans, the present work investigates avidin immunogenicity as part of risk/benefit evaluations. Sera from 139 oncology patients naive to avidin were confirmed to exhibit HAVA with lognormally distributed titers. HAVA were boosted after avidin treatment, with no correlation with the avidin dose or with the basal titer. No antibody-related clinical symptoms were observed in 21 HAVA-positive patients treated with avidin. In mouse models, high mouse antiavidin antibody titers, induced to simulate the worst human condition, neither reduced the biotin uptake of intratissue-injected avidin nor affected the capacity of intravenously injected avidin to clear a biotinylated drug from circulation. In both models the avidin treatment was well tolerated. Results indicate that avidin immunogenicity does not affect its safety and efficacy, thus encouraging its further use in clinical applications.
Petronzelli
Fiorella
F
R&D Immunology, Sigma-Tau SpA, Pomezia, Rome, Italy.
Pelliccia
Angela
A
Anastasi
Anna Maria
AM
Lindstedt
Ragnar
R
Manganello
Stefania
S
Ferrari
Liliana Elisa
LE
Albertoni
Claudio
C
Leoni
Barbara
B
Rosi
Antonio
A
D'Alessio
Valeria
V
Deiana
Katia
K
Paganelli
Giovanni
G
De Santis
Rita
R
D000818:Animals; D000906:Antibodies / Q000009:adverse effects* / Q000097:blood; D001360:Avidin / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use; D001710:Biotin / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009369:Neoplasms / Q000628:therapy*; D016499:Radioimmunotherapy / Q000009:adverse effects* / Q000379:methods; D014018:Tissue Distribution
D000906:Antibodies; D001360:Avidin; D001710:Biotin