Part II: Vaccines for haematological malignant disorders

Identification of an HLA-A1 restricted CTL epitope from Mcl-1

“…Apoptosis was originally defined as a mode of cell death with specific morphology. 1 Since the discovery of caspase proteases, it has been evident that caspase activation was indispensable for apotosis to occur in various mammalian cell types. First reports in the early 1990s demonstrated that the broad-spectrum caspase inhibitors such as z-VAD-fmk could effectively block apoptosis in several animal cell death models.…”

The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

“…The lower rates of relapse in allogeneic transplantation compared with autologous bone marrow transplantation, the striking clinical benefit of donorlymphocyte infusions as well as the finding that human T cells can destroy chemotherapy-resistant cell lines from chronic myeloid leukemia and multiple myeloma, have prompted development of immunotherapeutic strategies against haematological cancers [40]. Among these approaches, active specific immunization or vaccination is emerging as a valuable tool to boost the adaptive immune system against malignant cells.…”

Mcl-1 and anticancer vaccination: identification of an HLA-A2-restricted epitope

“…CXCL12 signals through CXCR4, a seven transmembrane, G-protein-coupled receptor, which is broadly expressed on a variety of normal cells, either belonging or not belonging to the hematopoietic system. 1 There is an extensive body of data concerning the prominent function of CXCL12 as a potent chemoattractant for various hematopoietic cells, including the CD34 þ hematopoietic progenitor cell (HPC); indeed, the CXCL12-CXCR4 axis is considered as the major player in the regulation of homing and retention of HPC in the marrow microenvironment. 1 In addition, CXCL12 interaction with CXCR4 expressed on tumor cells may favor their survival and growth in a paracrine manner, beyond promoting their metastatic spread in organs where the level of CXCL12 reaches a critical threshold.…”

“…1 There is an extensive body of data concerning the prominent function of CXCL12 as a potent chemoattractant for various hematopoietic cells, including the CD34 þ hematopoietic progenitor cell (HPC); indeed, the CXCL12-CXCR4 axis is considered as the major player in the regulation of homing and retention of HPC in the marrow microenvironment. 1 In addition, CXCL12 interaction with CXCR4 expressed on tumor cells may favor their survival and growth in a paracrine manner, beyond promoting their metastatic spread in organs where the level of CXCL12 reaches a critical threshold. 2 Acute myeloid leukemia (AML) cells express functional CXCR4 and respond to CXCL12 in a complex way that involves not only chemotaxis and migration beneath marrow stromal cells and to the peripheral blood (PB), but also the regulation of cell cycle progression.…”