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So we'll now be moving on
to another class of drugs
called immunomodulatory agents
and a few examples
in these class of drugs
are lenalidomide and pomalidomide.
So these drugs have
a unique class of action
and several pathways
have been recognized
as being involved that are targeted
by these novel group of agents.
Several investigators
have reported antiproliferative
and pro-apoptotic effects
of immunomodulatory agents
on tumor cells in vitro.
An important effect
of the immunomodulatory agents
is its ability to modulate production
of various cytokines
in the tumor microenvironment.
Lenalidomide is reported
to down regulate
key pro-survival cytokines
such as tumor necrosis factor,
the TNF alpha
and interleukin-6, interleukin-8,
and Vascular Endocrinal Growth Factor
or the VEGF.
Cytokines that enrich
the malignant microenvironment
favoring tumor cell survival
and proliferation
and resistance to therapy as well.
Lenalidomide may also affect
other components
of the tumor microenvironment
including
the immune cellular compartment.
The preclinical observations
demonstrate its activity
of immune effector cells
such as the T-cells and the NK cells,
stimulating T-cell proliferation
and increased production of IL-2
and interferon gamma
through T-cell receptor activation.
Also activation
and proliferation of NK cells
has been reported with lenalidomide.
So there is no one specific mechanism
of action of these agents
and with its varied mechanism
of actions,
it is unclear as to
if one particular pathway
is more active,
suggesting its better treatment
in either lymphomas or multiple myeloma
where it has received its approval
for multiple myeloma.
While lenalidomide is approved
in combination with the steroids
or other monoclonal antibodies
in multiple myeloma,
in lymphoma,
it's currently under investigation,
specifically in indolent lymphomas.
Lenalidomide is approved, however,
for mantle cell lymphoma
and in the next few slides
we will be discussing various studies
involving lenalidomide.
