Abstract 2396: IMA950: A novel multi-peptide cancer vaccine for treatment of glioblastoma

Abstract

Abstract Despite promising results of various therapeutic approaches currently under investigation, including active immunotherapy, glioblastoma (GBM) remains one of the most fatal tumor types. IMA950 is a novel peptide vaccine aiming at the induction of a broad T-cell response against a variety of tumor-relevant antigens expressed by GBM cells. IMA950 consists of 11 synthetic tumor-associated peptides (TUMAPs) isolated from more than 30 primary human GBM specimens. Nine of the TUMAPs bind to the human leukocyte antigen (HLA) class I allele A*02 expressed by ∼ 45% of the Caucasian population and two TUMAPs bind to various HLA class II (DR) alleles expressed by the majority of patients. Therefore, cytotoxic T-lymphocyte (CTL) as well as T helper (Th) responses are expected to arise from vaccination with IMA950. TUMAPs were identified by isolating HLA-peptide complexes from primary tumors and determining the peptide sequences by mass spectrometry. This analysis resulted in the identification of more than 3,000 different HLA-A*02 peptides expressed by one or more GBM samples. TUMAPs were ranked according to a variety of criteria, including mRNA over-expression of the source antigens in GBM compared with normal tissues, known relevance of the source antigens in oncogenic processes, frequency of expression in GBM samples, in vitro immunogenicity in healthy donors, and feasibility of pharmaceutical development. Based on this approach IMA950 has been composed of 11 TUMAPs derived from 10 different source antigens ranking high in these categories. “Over-presentation” of finally selected TUMAPs was confirmed directly at the peptide level using a novel approach allowing label-free HLA-peptide quantitation directly by mass spectrometry. Moreover, T-cell reactivity in glioma patients was analyzed for all HLA-A*02 peptides in vitro with all patients tested responding to several IMA950 TUMAPs. Furthermore, peptide-specific functions of the observed T cells were investigated in more detail. In conclusion, the strong GBM association of IMA950 TUMAPs indicated by over-presentation together with pre-clinical immunogenicity results suggest that this multi-peptide vaccine may benefit the majority of HLA-A*02-positive patients. Clinical development is planned to start within 2010 with several phase I trials investigating the safety and immunogenicity of the vaccine in different patient populations and using various immunomodulatory regimens in order to explore the most promising strategy for further development. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2396.