The Selection of Aptamers to CD20 and Their Application as Inhibitors of Complement Dependent Cytotoxicity

CD20 is an important oncological B-cell marker. Immunotherapy, using anti-CD20 antibodies, has revolutionized the treatment of B-cell cancers. Aptamers are highly specific DNA ligands, raised to identify virtually any target molecule through an iterative process known as SELEX (systematic evolution of ligands by exponential amplification). Aptamers rival antibodies in both binding affinity and specificity. We developed a novel CD20 specific SELEX method, using a lentiviral system to transfect CD20 cDNA into HEK293 cells. Selection using CD20+HEK cells evolved pools of aptamers with stepwise increases in binding affinity for the transfected cell line. Sequenced aptamer clones exhibited an antagonistic effect with anti-CD20 antibody; and in a biological assay possessed a protective capacity, limiting the extent of antibody induced complement dependent cytotoxicity. Overall, genetic transfection is a novel targeted approach of ligand generation, producing aptamers endowed with both physical and biological capabilities

Name thesis:degree_name

MSc

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Sciences / Science

Grantor dc:publisher

Université d'Ottawa / University of Ottawa

Year dc:date.issued

2015

Author dc:creator

• Al-Youssef, Nadia

Advisor dc:contributor.supervisor

• Berezovski, Maxim

• aptamer
• CD20

Language dc:language.iso

en

Identifier URI

http://dx.doi.org/10.20381/ruor-4060

Identifier

http://dx.doi.org/10.20381/ruor-4060

OAI record oai:identifier

https://ruor.uottawa.ca/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Aruor.uottawa.ca%3A10393%2F33182