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  • Nanoparticle Enhancement of CCL21 Immunotherapy Treatment for Glioblastoma Demonstrates a Synergistic Anti-Tumor Effect

    Final Number:
    1524

    Authors:
    Panayiotis Emmanuel Pelargos B.A.; Nikhilesh Bhatt; Jacky Chen; Mark Libowitz; Natalie E Barnette; Linda M. Liau MD, PhD; Robert M. Prins PhD; Valerie Kickhoeffer; Leonard Rome; Isaac Yang MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: Glioblastoma (GBM) is the one of the most common and deadliest primary brain tumors. Nanotechnology has emerged as a viable treatment effector that can mediate antitumor activity. The lymphoid chemokine CCL21 is a chemoattractant for mature dendritic cells, naïve and memory T cells, and natural killer cells. CCL21 packaged in the vault nanoparticle (CCL21-nanoparticle) may decrease tumor growth and enhance lymphocyte infiltration.

    Methods: In our pre-clinical model, GL261 cells (1.0 x 106) were implanted subcutaneously into the flank of 6-week-old C57BL/6 mice. The mice were treated with five intratumoral injections of CCL21-nanoparticle, vault nanoparticle alone, or CCL21 chemokine alone. Tumor size was measured at bisecting angles with calipers. At study conclusion, the presence and number of lymphocytes in tumors were analyzed using flow cytometry.

    Results: The CCL21-nanoparticle treatment group demonstrated a significant decrease in tumor growth rate when compared to CCL21 alone and nanoparticle alone. The fold change in tumor area in the CCL21-nanoparticle group was 4.3 compared to 5.2 and 6.4 for the vault nanoparticle group and CCL21 group, respectively. CCL21-nanoparticle treatment also increased CD3+ lymphocyte infiltrates in the tumor.

    Conclusions: This data suggests that CCL21-vaults can hinder tumor growth and promote lymphocyte antitumor activity in this pre-clinical model. Furthermore, our data demonstrates that nanoparticle delivery enhances the immunotherapeutic effect of CCL21. Further studies are needed to fully elucidate the synergy of combining chemokines with nanoparticles for targeted tumor therapy.

    Patient Care: It provides evidence of the efficacy of nanoparticle delivery of the chemokine CCL21 to enhance the antitumor effects of the patient’s own immune system.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of nanoparticle delivery of CCL21 to enhance antitumor effects, 2) Discuss, in small groups, the future potential for nanoparticle delivery of treatments, 3) Identify an effective treatment for GBM.

    References:

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