TY - JOUR
T1 - Nanoformulation of CCL21 greatly increases its effectiveness as an immunotherapy for neuroblastoma
AU - Poelaert, Brittany J.
AU - Romanova, Svetlana
AU - Knoche, Shelby M.
AU - Olson, Madeline T.
AU - Sliker, Bailee H.
AU - Smits, Kaitlin
AU - Dickey, Brittney L.
AU - Moffitt-Holida, Alexandra E.J.
AU - Goetz, Benjamin T.
AU - Khan, Nuzhat
AU - Smith, Lynette
AU - Band, Hamid
AU - Mohs, Aaron M.
AU - Coulter, Donald W.
AU - Bronich, Tatiana K.
AU - Solheim, Joyce C.
PY - 2020/11/10
Y1 - 2020/11/10
N2 - 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. Thus, this novel nanoformulation of CCL21 is an effective treatment for neuroblastoma, and may have potential for the delivery of CCL21 to other types of solid tumors in the future and as a slow-release delivery modality for other immunotherapies
AB - 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. Thus, this novel nanoformulation of CCL21 is an effective treatment for neuroblastoma, and may have potential for the delivery of CCL21 to other types of solid tumors in the future and as a slow-release delivery modality for other immunotherapies
KW - CCL21
KW - Cancer
KW - Immunotherapy
KW - Nanoformulation
KW - Nanoparticle
KW - Neuroblastoma
UR - http://www.scopus.com/inward/record.url?scp=85089502766&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089502766&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2020.07.024
DO - 10.1016/j.jconrel.2020.07.024
M3 - Article
C2 - 32711026
AN - SCOPUS:85089502766
VL - 327
SP - 266
EP - 283
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -