Identifying Immunogenic CD4+ T-cell Epitopes of Myeloid Cell Leukemia 1 Using Overlapping 20-mer Peptides Spanning the Whole Protein

摘要

Myeloid cell leukemia 1 (Mcl-1) is an anti-apoptotic protein which is overexpressed in various leukemia and other cancers [1]. Mcl-1 has a very short half-life [2], which has been suggested as a molecular mechanism for cells to switch into either the survival or apoptotic pathways in response to different stresses [3]. Recently, it has been demonstrated that downregulation of Mcl-1 by various pharmacological agents or genetic approaches dramatically increases ABT-737 lethality in various malignant cell types [4]. Different strategies for targeting Mcl-1 include (i) small interfering RNA [5] (ii) small-molecule inhibitors [6] and (iii) peptide inhibitors [7] In recent years, therapeutic vaccination with synthetic peptides derived from anti-apoptotic proteins such as Mcl-1 has emerged as a promising strategy against hematological cancers. In this study, 34 overlapping 20-mer peptides, spanning the entire Mcl-1 protein, were adjuvanted with cationic liposomes [8] and tested in three different mouse strains with varied Major Histocompatibility Complex (MHC) haplotypes (FVB [H-2q], CB6Fl[H-2b/d], B6CBAF1 [H-2b/k]) to identify immunogenic CD4+ T-cell epitopes.