Abstract
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], CB6F1[H-2b/d], B6CBAF1 [H-2b/k])
to identify immunogenic CD4+ T-cell epitopes.
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], CB6F1[H-2b/d], B6CBAF1 [H-2b/k])
to identify immunogenic CD4+ T-cell epitopes.
| Originalsprog | Engelsk |
|---|---|
| Titel | Proceedings of the 24th American Peptide Symposium Ved Srivastava, Andrei Yudin, and Michal Lebl (Editors) American Peptide Society |
| Antal sider | 2 |
| Publikationsdato | 2015 |
| Sider | 262-63 |
| Status | Udgivet - 2015 |
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