IT-06 * PERSONALIZED IMMUNOTHERAPY FOR THE TREATMENT OF GLIOBLASTOMA

Abstract

BACKGROUND: Immunotherapy harnesses the immune system to specifically attack malignant cells thereby offering a targeted treatment option without systemic toxicity for patients with GBM. However, immunotherapy remains limited by the relative dearth of antigen specific tumor targets. Since GBMs have been shown to express cytomegalovirus (CMV) antigens, we can use these viral epitopes as a novel, effective, and specific targets in conjunction with other tumor associated antigens (TAAs) for effective glioma therapy. We hypothesize that elucidating a more full antigenic profile of CMV and other TAAs for use in a multi-component immunotherapeutic approach will provide robust immunologic responses against GBM. METHODS: We designed a multiplex RT-qPCR SYBR array (Bio-Rad) containing 27 CMV genes that were shown to be associated with immune reactivity. Agilent 4x44k custom gene expression arrays were designed and developed to screen GBM patient tumor samples for the presence of human TAA genes. RT-qPCR products were verified via Sanger sequencing and select TAA microarray genes were validated via RT-qPCR. Targets identified within GBM specimens were evaluated for immunogenicity in vitro using RNA-pulsed dendritic cells. RESULTS/CONCLUSIONS: As expected, there was significant heterogeneity in the expression of CMV and TAA antigens within primary GBM tumors. The capacity to effectively target GBM tumors using autologous T cells stimulated by antigen pulsed DCs was demonstrated in vitro. In summary, given differences in antigenic profiles of GBM patients, a personalized targeted approach will allow us to select the appropriate RNA transcripts for use in a multi-component dendritic cell based therapy. The enrichment for personalized tumor antigens using transcript specific autologous RNA amplification may further refine immunologic targeting and we have demonstrated the feasibility and immunologic potency of this novel therapeutic approach.