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Aptamer‐Drug Conjugates for Targeted Therapy of CD30‐expressing Lymphomas
Author(s) -
Parekh Parag A,
Kamble Sanchit R,
Zihua Zeng,
Zu Youli
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1088.5
Subject(s) - aptamer , cd30 , conjugate , in vivo , chemistry , systematic evolution of ligands by exponential enrichment , targeted therapy , lymphoma , anaplastic large cell lymphoma , targeted drug delivery , cancer research , microbiology and biotechnology , brentuximab vedotin , selex aptamer technique , antibody drug conjugate , pharmacology , drug , biology , rna , biochemistry , antibody , cancer , monoclonal antibody , immunology , gene , mathematics , mathematical analysis , genetics
CD30 is a biomarker for diagnosis and targeted therapy of Anaplastic Large cell lymphoma (ALCL) and Classical Hodgkin Lymphoma (CHL). Our previous studies have demonstrated specific binding of RNA aptamer to CD30 positive tumor cells. However, for in vivo targeted therapy there is a concern about biostability of the RNA aptamers. To overcome this, an ssDNA aptamer was developed via a hybrid SELEX approach using CD30‐expresing lymphoma cells and purified CD30 protein to yield the aptamer C2NP which specifically bound to CD30 expressing ALCL and CHL cells at concentrations ≤10 nm and did not react to control tumor cells. Importantly, C2NP is highly stable and more than 50% of them remained after incubation in human serum at 37°C for 24 hours, indicating the suitability for in vivo use. For targeted therapy study, C2NP was conjugated with a chemotherapeutic agent and a fluorescent reporter to form an aptamer‐drug conjugate (ADC). The specificity of ADC was confirmed by flow cytometry and intracellular delivery of chemo‐drug was observed by microscopy. Chemical conjugation of drug had no effect on aptamer binding specificity and affinity to lymphoma cells. In addition, potential therapeutic effects of the aptamer‐drug conjugate are under investigation by using cultured ALCL and CHL cell‐lines currently. This is the first study to use an aptamer‐drug conjugate for targeted therapy of CD30‐exprssing lymphomas.