Abstract 4754: Type-1 dendritic cell vaccines in combination with poly-ICLC-association between positive tetramer response and 6-month progression-free survival in patients with recurrent malignant glioma
Authors: Okada Hideho , Lieberman Frank S. , Hoji Aki , Kalinski Pawel , Mintz Arlan H. , Engh Johnathan A. , Park Deric M. , Bartlett David L. , Zeh Herbert , Whiteside Theresa L. , Butterfield Lisa H. , Hamilton Ronald L. , Salazar Andres M. , Pollack Ian F. 
Published: February 2011

Our previous preclinical studies have demonstrated that intramuscular (i.m.) administration of a Toll-like receptor 3 ligand poly-ICLC remarkably enhances induction of type-1 cytotoxic T-lymphocytes (CTLs) and improves therapeutic efficacy of vaccinations against glioma-associated antigen (GAA)-derived CD8+ T cell epitopes. The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of vaccinations with Type-1 α dendrititc cells (αDC1) loaded with glioma associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas.

Human leukocyte Antigen (HLA)-A2+ participants with recurrent malignant glioma received intra-lymph-node injections of type-1 dendritic cells (DCs) loaded with HLA-A2 binding GAA-peptides EphA2 (883-891), IL-13Ralpha2 (345-353:1A9V), YKL-40 (202-211) and GP100 (209-217: 2M) at two-week intervals. Participants also received twice weekly i.m. injections of 20 µg/kg poly-ICLC. Participants who demonstrated positive radiological response or stable disease without major adverse events were allowed to receive booster vaccines. Primary endpoints were assessments of safety and immunological responses by ELISPOT and tetramer assays. Clinical and radiological responses were also evaluated.

To date, 19 participants (12 with glioblastoma multiforme [GBM], 4 with anaplastic astrocytoma [AA] and 3 anaplastic oligodendroglioma [AO]) have received at least 4 vaccinations with no major adverse events. Increased CD8+ cells reactive to EphA2- or IL-13Rα2-tetramers were detected in post-vaccine peripheral blood mononuclear cells (PBMC) in 9 of 11 participants evaluated. Some of these patients also demonstrated up-regulation of a chemokine receptor CXCR3 on CD8+ PBMC following vaccines, indicating that the vaccine regimen induced type-1 CTL responses. Six patients achieved progression free at 6 months (3 GBM, 2AA and 1 AO). Among these, 3 patients are currently progression free at 23 (AA), 20 (AA) or 9 (GBM) months after the first vaccine, and receiving booster vaccines every 3 months. Although the trial enrolled mixed tumor types, Fisher's exact test indicated an association between positive tetramer response and 6-month progression-free survival, suggesting a possible correlation between antigen-specific responses and clinical response.

These interim data demonstrate preliminary safety, immunological and clinical activity of poly-ICLC-assisted type-1 DC-based vaccines.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4754.