Sunday, November 30, 2014 1:52:20 AM
PS Targeting decreases MDSC's and MDSC's have been found to be a blood based biomarker for disease progression and abnormal high counts of MDSC's lead to decreased overall survival. I just wanted to make that clear for those that do not see the words Peregrine Pharmaceuticals or Bavituximab in the following, though if one follows Peregrine Pharmaceuticals... its quite easy to understand that Bavituximab is a PS Targeting Mab with astronomical value if you are able to connect the dots.
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Myeloid derived suppressor cells in multiple myeloma: preclinical research and translational opportunities
Cirino Botta1, Annamaria Gullà1, Pierpaolo Correale2, Pierosandro Tagliaferri1 and Pierfrancesco Tassone1*
1"Magna Graecia" University of Catanzaro, Italy
2Siena University Hospital, Italy
Received: 13 Oct 2014; Paper pending published: 16 Nov 2014;
Accepted: 23 Nov 2014.
Edited by:
ALESSANDRA ROMANO, University of Catania, Italy
Reviewed by:
Peiman Hematti, University of Wisconsin-Madison, USA
Qaiser Bashir, The University of Texas MD Anderson Cancer Center, USA
Immunosuppressive cells have been reported to play an important role in tumor progression mainly because of their capability to promote immune-escape, angiogenesis and metastasis. Among them, myeloid derived suppressor cells (MDSCs) have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr-1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM) of multiple myeloma (MM) patients with a role in disease progression and/or drug resistance. Preclinical models recapitulating the complexity of the MM-related BM microenvironment (BMM) are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs) and for the development of new agents targeting MM-associated immune suppressive cells.
This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM.
Concluding remarks
During the last decade a growing effort has been devoted to understanding the role of MM-driven immunosuppression in reducing or preventing the efficacy of immunotherapy. Among others, MDSCs revealed to play a critical role in the generation of such immune dysfunctional microenvironment in different animal models and cancer patients. On these bases it is possible to speculate that the identification of molecular pathways involved in MDSC function will lead to the development of new tailored agents able to disrupt the tumor-host immunosuppressive interactions, thus improving the efficacy of both humoral and cellular immunotherapy.
We now predict a new era for immunotherapy in MM which will provide breakthrough improvements in the treatment of this important still incurable disease.
http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00348/abstract
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Looks like Dmitry Gabrilovich is headed into one of the most cited authors list re: MDSC's in 2014/2015 and this is like that snow ball that continues to grow. Looks like the Italians are liking what they see in researching MDSC's
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Myeloid derived suppressor cells in multiple myeloma: preclinical research and translational opportunities
Cirino Botta1, Annamaria Gullà1, Pierpaolo Correale2, Pierosandro Tagliaferri1 and Pierfrancesco Tassone1*
1"Magna Graecia" University of Catanzaro, Italy
2Siena University Hospital, Italy
Received: 13 Oct 2014; Paper pending published: 16 Nov 2014;
Accepted: 23 Nov 2014.
Edited by:
ALESSANDRA ROMANO, University of Catania, Italy
Reviewed by:
Peiman Hematti, University of Wisconsin-Madison, USA
Qaiser Bashir, The University of Texas MD Anderson Cancer Center, USA
Immunosuppressive cells have been reported to play an important role in tumor progression mainly because of their capability to promote immune-escape, angiogenesis and metastasis. Among them, myeloid derived suppressor cells (MDSCs) have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr-1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM) of multiple myeloma (MM) patients with a role in disease progression and/or drug resistance. Preclinical models recapitulating the complexity of the MM-related BM microenvironment (BMM) are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs) and for the development of new agents targeting MM-associated immune suppressive cells.
This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM.
Concluding remarks
During the last decade a growing effort has been devoted to understanding the role of MM-driven immunosuppression in reducing or preventing the efficacy of immunotherapy. Among others, MDSCs revealed to play a critical role in the generation of such immune dysfunctional microenvironment in different animal models and cancer patients. On these bases it is possible to speculate that the identification of molecular pathways involved in MDSC function will lead to the development of new tailored agents able to disrupt the tumor-host immunosuppressive interactions, thus improving the efficacy of both humoral and cellular immunotherapy.
We now predict a new era for immunotherapy in MM which will provide breakthrough improvements in the treatment of this important still incurable disease.
http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00348/abstract
--------------------------
Looks like Dmitry Gabrilovich is headed into one of the most cited authors list re: MDSC's in 2014/2015 and this is like that snow ball that continues to grow. Looks like the Italians are liking what they see in researching MDSC's
"Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that is the cornerstone of a broad clinical
pipeline." -- Big Pharmas nightmare... unless they are fortunate enough to have The Bavi Edge!
