Biology Reference
In-Depth Information
Undoubtedly, more evidence will be amassed regarding the use of TNF for
GVHD prophylaxis and therapy in the coming years, but it is important
to recognize that other cytokine-directed therapies are also likely to have
important roles in the future. The preclinical evidence for IL-6 blockade is
strong, and trial results will reveal its ongoing role. IL-21 and the related
cytokine IL-17 are also promising targets for post-transplant blockade, and
again, trial results will confirm whether these mechanistically promising
targets can be safely and effectively used after transplantation in the clini-
cal setting.
In terms of cytokine administration, there is clear preliminary evidence for
IL-2 administration after BMT, and further, large-scale trials will determine
the overall capacity of this therapy to reduce GVHD by the purported Treg
expansion that ensues from IL-2 administration.
BOX 16.1
Specific cytokine-directed GVHD therapies
Drug
Mechanism of action
Etanercept
(TNFR:FC)
TNFR p75 fused to FC protein.
Acts to bind soluble TNF and LT
α
, thus neutral-
izing their action.
Is not thought to bind memTNF or memLT
α
/
β
heterotrimers—and this is in contrast to the
anti-TNF monoclonal antibodies (e.g., Inflix-
imab), which are known to deplete effector
T cells on the basis of memTNF expression.
381
Tocilizumab (anti
IL-6R)
Humanized mAb to the IL-6 receptor
α
.
Approved for RA treatment.
Neutralizes proinflammatory effects of IL-6.
IL-2 cytokine
Signaling via physiological IL-2R.
Expansion of Treg populations, due to their ex-
pression of the “high-affinity” IL-2R and there-
fore susceptibility to the lowest physiological
IL-2 concentrations.
Recombinant
IFN-
α
Enhances sensitivity of tumor cells to cytolysis.
Enhances CTL function.
The “CSFs”
G-CSF is the most prevalent cytokine in cur-
rent clinical use and has the dual roles of donor
mobilization and subsequent immunomodula-
tory effects on the ingoing graft.
GM-CSF has been used historically—and may
be used again in the future to expand protec-
tive/regulatory donor DC populations.
CSF-1 administration may be useful for expan-
sion of protective myeloid cells prior to trans-
plant.
Search WWH ::
Custom Search