TY - JOUR
T1 - Therapeutic use of avidin is not hampered by antiavidin antibodies in humans
AU - Petronzelli, Fiorella
AU - Pelliccia, Angela
AU - Anastasi, Anna Maria
AU - Lindstedt, Ragnar
AU - Manganello, Stefania
AU - Ferrari, Liliana Elisa
AU - Albertoni, Claudio
AU - Leoni, Barbara
AU - Rosi, Antonio
AU - D'Alessio, Valeria
AU - Deiana, Katia
AU - Paganelli, Giovanni
AU - De Santis, Rita
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
KW - antibody
KW - avidin
KW - HAVA
KW - immunogenicity
KW - radioimmunotherapy
KW - targeted therapy
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UR - http://www.scopus.com/inward/citedby.url?scp=77958155248&partnerID=8YFLogxK
U2 - 10.1089/cbr.2010.0797
DO - 10.1089/cbr.2010.0797
M3 - Article
C2 - 20863248
AN - SCOPUS:77958155248
VL - 25
SP - 563
EP - 570
JO - Cancer Biotherapy and Radiopharmaceuticals
JF - Cancer Biotherapy and Radiopharmaceuticals
SN - 1084-9785
IS - 5
ER -