Nanoformulation of CCL21 greatly increases its effectiveness as an immunotherapy for neuroblastoma

Brittany J. Poelaert, Svetlana Romanova, Shelby M. Knoche, Madeline T. Olson, Bailee H. Sliker, Kaitlin Smits, Brittney L. Dickey, Alexandra E.J. Moffitt-Holida, Benjamin T. Goetz, Nuzhat Khan, Lynette Smith, Hamid Band, Aaron M. Mohs, Donald W. Coulter, Tatiana K. Bronich, Joyce C. Solheim

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Neuroblastoma is the most commonly diagnosed extracranial solid tumor in children. The patients with aggressive metastatic disease or refractory/relapsed neuroblastoma currently face a dismally low chance of survival. Thus, there is a great need for more effective therapies for this illness. In previous studies, we, as well as others, showed that the immune cell chemoattractant C-C motif chemokine ligand 21 (CCL21) is effective as an intratumoral therapy able to slow the growth of cancers. In this current study, we developed and tested an injectable, slow-release, uniform, and optimally loaded alginate nanoformulation of CCL21 as a means to provide prolonged intratumoral treatment. The alginate-nanoformulated CCL21, when injected intratumorally into mice bearing neuroblastoma lesions, significantly prolonged survival and decreased the tumor growth rate compared to CCL21 alone, empty nanoparticles, or buffer. Notably, we also observed complete tumor clearance and subsequent full protection against tumor rechallenge in 33% of nanoformulated CCL21-treated mice. Greater intratumoral presence of nanoformulated CCL21, compared to free CCL21, at days 1 and 2 after treatment ended was confirmed through fluorescent labeling and tracking. Nanoformulated CCL21-treated tumors exhibited a general pattern of prolonged increases in anti-tumor cytokines and relatively lower levels of pro-tumor cytokines in comparison to tumors treated with CCL21 alone or buffer only.

Original languageEnglish (US)
Pages (from-to)266-283
Number of pages18
JournalJournal of Controlled Release
StatePublished - Nov 10 2020


  • CCL21
  • Cancer
  • Immunotherapy
  • Nanoformulation
  • Nanoparticle
  • Neuroblastoma

ASJC Scopus subject areas

  • Pharmaceutical Science


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