Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer

Biomaterials. 2013 Nov;34(35):8909-17. doi: 10.1016/j.biomaterials.2013.07.099. Epub 2013 Aug 19.

Abstract

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.

Keywords: ALCL; CD30; Cancer immunotherapy; Lymphoma; cHL; ssDNA aptamer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis
  • Aptamers, Nucleotide / genetics
  • Aptamers, Nucleotide / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • HL-60 Cells
  • Hodgkin Disease / genetics
  • Hodgkin Disease / pathology
  • Humans
  • Immunotherapy / methods*
  • K562 Cells
  • Ki-1 Antigen / genetics
  • Ki-1 Antigen / metabolism*
  • Lymphoma, Large-Cell, Anaplastic / genetics
  • Lymphoma, Large-Cell, Anaplastic / pathology*
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Sequence Analysis, DNA
  • Signal Transduction

Substances

  • Aptamers, Nucleotide
  • Ki-1 Antigen