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Re: biopharm post# 248471

Saturday, 01/16/2016 1:30:08 AM

Saturday, January 16, 2016 1:30:08 AM

Post# of 347009
Dmitry Gabrilovich : Peregrine Pharmaceuticals KOL :

.... we know PS targeting causes a statistically significant reduction of MDSC's and Dmitry Gabrilovich being a KOL and backer of PS Targeting....hmmmmm : )

Bone marrow PMN-MDSCs and neutrophils are functionally similar in protection of multiple myeloma from chemotherapy

Indu R. Ramachandran
Thomas Condamine
Cindy Lin
Sarah E. Herlihy
Alfred Garfall
Dan Toby Vogl

Cancer letters (Impact Factor: 5.62). 11/2015; 371(1). DOI: 10.1016/j.canlet.2015.10.040

ABSTRACT
Multiple myeloma (MM) is an incurable cancer of plasma cells localized preferentially in the bone marrow (BM). Resistance to chemotherapy represents one of the main challenges in MM management. BM microenvironment is known to play a critical role in protection of MM cells from chemotherapeutics; however, mechanisms responsible for this effect are largely unknown. Development of MM is associated with accumulation of myeloid-derived suppressor cells (MDSCs) mostly represented by pathologically activated relatively immature polymorphonuclear neutrophils (PMN-MDSCs). Here, we investigated whether PMN-MDSCs are responsible for BM microenvironment-mediated MM chemoresistance. Using in vivo mouse models allowing manipulation of myeloid cell number, we demonstrated a critical role for myeloid cells in MM growth and chemoresistance. PMN-MDSCs isolated from MM-bearing host are immunosuppressive and thus, functionally distinct from their counterpart in tumor-free host neutrophils. We found, however, that both PMN-MDSCs and neutrophils equally promote MM survival from doxorubicin and melphalan and that this effect is mediated by soluble factors rather than direct cell-cell contact. Our data indicate that targeting PMN-MDSCs would enhance chemotherapy efficacy in MM.

https://www.researchgate.net/publication/284913839_Bone_marrow_PMN-MDSCs_and_neutrophils_are_functionally_similar_in_protection_of_multiple_myeloma_from_chemotherapy


"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!

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