EXTH-27. TRANSLATABLE CCL3 THERAPY TO PROMOTE DC VACCINE MIGRATION AND EFFICACY AGAINST GLIOMA
نویسندگان
چکیده
Abstract INTRODUCTION Prior evidence from our studies have identified chemokine ligand 3 (CCL3) as a key modulator to increase DC vaccine migration draining lymph nodes (VDLNs) which is associated with improved long-term survival clinically. METHODS The effect of CCL3 treatment on ex vivo and in (n=5), antigen-specific T cell responses efficacy against orthotopic GL261-OVA SMA560 tumors (n=10) was studied C57Bl/6 VMdK mice. mouse human vaccines also tested transwell assays. DCs were electroporated OVA-mRNA or pulsed ODC1 neoantigen peptide. quantified by flow cytometry. Median overall (mOS) measure days (d) post-intracranial implantation. RESULTS Ex-vivo 20ng/mL (18 1hr pre-injection) increased (mouse human) VDLN. In systemic resulted dose-dependent VDLN (10µg, 20µg, 50µg). added vaccination generated more tumor CD8+IFNγ+ cells at 7-days. antigen-DC significantly greater compared OVA-DC alone (GL261-OVA: mOS DCvac: 19.5d, CCL3+DCvac 37d, p=0.0174; SMA560: mOS: 25d, CCL3+DCvac: 48d, p=0.002). CONCLUSIONS These data combined previous success clinical trials reflect the potency enhance vaccine-specific migration, immune responses, survival. novel safe adjuvant overcome prior limitations therapy may be translatable heterogeneous antigen presentation following vaccine-targeted killing. used drug could without potential toxicity patients glioblastoma.
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ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.826