ABSTRACT
As a "chemical antibody", oligonucleotide aptamers can specifically bind to their target molecules. However, clinical potential of aptamers in disease diagnosis is not yet fully explored. Using a tumor cell-based selection protocol, we developed single-stranded DNA aptamers for Hodgkin lymphoma (HL) tumor cells. The aptamers specifically bound to HL cells with a high affinity, reaching maximal cell binding at 10 nM final concentration. Importantly, the aptamers were able to selectively detect HL cells and did not react to other tumor or blood cells in mixed samples, indicating that the aptamers can be used as a specific probe for in vitro analysis of HL cells. Moreover, due to the inherent properties of DNA, the aptamers were stable in human serum, suggesting potential for in vivo detection of HL tumor cells.
Subject(s)
DNA, Single-Stranded/genetics , Hodgkin Disease/diagnosis , Aptamers, Nucleotide/genetics , Hodgkin Disease/genetics , Humans , SELEX Aptamer Technique/methodsABSTRACT
CD30 is highly expressed on Hodgkins lymphoma and anaplastic large cell lymphoma, making it an attractive target for therapy. We describe the generation of serum-stabilized ssDNA aptamers that bind CD30 via a hybrid SELEX methodology. The selected aptamer bound CD30 with high affinity and specificity. Further optimization of the aptamer led to a short, truncated variant with a 50-fold higher affinity than its longer counterpart. The multivalent aptamer was able to induce oligomerization of CD30 receptors and, in effect, activate downstream signaling, which led to apoptosis of ALCL cells. Immunotherapy using aptamer-based co-stimulation provides an alternative to antibodies, and has potential to transform cancer treatment.
