Determining the effects of CCL21 nanomedicine therapeutic modalities in cancer

Abstract

Abstract Solid tumors demonstrate varying levels of immunogenic potential as well as the proficiency to undergo immune evasion, thus there is a need for novel therapies capable of augmenting the patient’s anti-tumor immune response in a concentrated and durable manner. We hypothesized that therapeutic modalities utilizing the chemoattractant C-C motif chemokine ligand 21 (CCL21) in a novel alginate nanoformulation will provide prolonged release of CCL21 and subsequent steady infiltration of immune cells into the tumor, which will abrogate disease progression and delay tumor growth significantly better than CCL21 alone. Nanoformulations of CCL21 were first analyzed for rates of release in vitro. We found that intratumoral administration of nanoformulation CCL21 significantly prolonged the survival of A/J mice with subcutaneous neuroblastoma tumors, compared to controls. Furthermore, we also determined that the tumor growth rate for nanoformulation CCL21-treated mice was significantly lower in comparison to the tumor growth rates of mice treated with buffer control, empty nanoparticles, or CCL21 alone. Notably, four out of nine nanoformulation CCL21-treated mice demonstrated complete tumor regression. When rechallenged, these four mice failed to produce tumors within a two-week period, therefore suggesting that a protective memory immune response had been induced by the nanoformulation CCL21 treatment. These results indicate that nanoformulation CCL21 therapy may be clinically relevant for the treatment of children and adolescents diagnosed with neuroblastoma. In addition, this novel nanoformulation may also have potential for future development as a means for slow-release delivery of other immunotherapies besides CCL21.