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2017 ; 4
(ä): 31-40
Nephropedia Template TP
gab.com Text
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English Wikipedia
Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone
Marrow Transplant Leukocytes to Enhance Graft versus Tumor
#MMPMID28345022
Lilly CL
; Villa NY
; Lemos de Matos A
; Ali HM
; Dhillon JS
; Hofland T
; Rahman MM
; Chan W
; Bogen B
; Cogle C
; McFadden G
Mol Ther Oncolytics
2017[Mar]; 4
(ä): 31-40
PMID28345022
show ga
Allogeneic stem cell transplant-derived T cells have the potential to seek and
eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma
virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like
multiple myeloma (MM) and can arm transplant-derived T cells to become more
effective cancer killers in vitro and in an immunodeficient xenotransplant murine
model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in
immunocompetent mice using an allogeneic mouse-mouse model. In contrast to all
human MM cell lines previously tested, the murine MM cell line tested here was
highly resistant to direct MYXV infection and oncolysis in vitro. Despite this
in vitro resistance, we found that ex vivo MYXV-armed allogeneic bone marrow (BM)
transplantation dramatically ablated pre-seeded residual MM in vivo.
Unexpectedly, we show that both neutrophils and activated T cells from the donor
function as virus-armed carrier cells, and MYXV-preloaded cells enhanced MM
killing. Our results demonstrate a novel therapeutic paradigm for residual
cancer, in which multiple classes of allotransplant leukocytes can be armed by
MYXV ex vivo to enhance the graft-versus-tumor effects.