Cancer-associated CD43 glycoforms as target of immunotherapy

Franca Maria Tuccillo, Camillo Palmieri, Giuseppe Fiume, Annamaria De Laurentiis, Marco Schiavone, Cristina Falcone, Enrico Iaccino, Ricciarda Galandrini, Cristina Capuano, Angela Santoni, Francesco Paolo D'Armiento, Claudio Arra, Antonio Barbieri, Fabrizio Dal Piaz, David Venzon, Patrizia Bonelli, Franco Maria Buonaguro, Iris Scala, Massimo Mallardo, Ileana QuintoGiuseppe Scala

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Abstract

CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with antitumor activity in vivo because its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T cells in mice. Furthermore, we demonstrate that tumor inhibition was due to UN1 mAb-dependent natural killer-mediated cytotoxicity. By screening a phage-displayed random peptide library, we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harbored a peptide sequence that was specifically recognized by the UN1 mAb and inhibited the binding of the UN1 mAbto UN1-positive tumor cells. On the basis of sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility of using monoclonal antibodies to identify cancer-associated mimotopes for immunotherapy.

Original languageEnglish
Pages (from-to)752-762
Number of pages11
JournalMolecular Cancer Therapeutics
Volume13
Issue number3
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tuccillo, F. M., Palmieri, C., Fiume, G., De Laurentiis, A., Schiavone, M., Falcone, C., Iaccino, E., Galandrini, R., Capuano, C., Santoni, A., D'Armiento, F. P., Arra, C., Barbieri, A., Dal Piaz, F., Venzon, D., Bonelli, P., Buonaguro, F. M., Scala, I., Mallardo, M., ... Scala, G. (2014). Cancer-associated CD43 glycoforms as target of immunotherapy. Molecular Cancer Therapeutics, 13(3), 752-762. https://doi.org/10.1158/1535-7163.MCT-13-0651