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Novo Annual Review 2016
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collect
cell
s
from patient 1
cell
infusion 4
cell
expansion 3 activate
cell
s
2 produce and actively sustain high levels of adenosine within the tumour micro-environment. the adenosine that tumours produce interacts with adenosine receptors on the surface of invading
immune
cell
s
. a type of adenosine receptor known as a2a is expressed on several
cell
s
of the
immune
system, including t-
cell
s
, nk
cell
s
, macrophages and dendritic
cell
s
. binding of adenosine to the a2a receptor has the effect of limiting the
immune
cell
s
? ability to attack tumours. a significant body of scientific data indicates that blocking a2a receptor can promote anti-tumour
immune
responses, leading to tumour regression. cpi-444 is an orally administered antagonist of the adenosine a2a receptor. the molecule entered a phase 1b study in early 2016. in collaboration with genentech, this study is evaluating cpi-444 as a single agent and in combination with another promising checkpoint inhibitor. nkarta ? harnessing the ?natural killing? capabilities of nk
cell
s
nkarta therapeutics is focused on developing therapies using natural killer (nk)
cell
s
. nkarta?s core capability, developed by scientific founder dario campana, is the consistent expansion and genetic modification of primary nk
cell
s
for adoptive
cell
immunotherapy (for an overview of this process, please see fig. 3). nk
cell
s
have an intrinsic ability to distinguish transformed versus normal
cell
s
. nk
cell
s
are unique based on the following attributes: ? they do not require activation to kill
cell
s
that are missing ?self? markers. this is especially important because harmful
cell
s
that are missing ?self? markers cannot be detected and destroyed by other
immune
cell
s
, such as t-
cell
s
. ? they express both activating and inhibitory receptors that recognise multiple ligands, a potential advantage relative to the recognition of a single antigen seen with t-
cell
s
. ? they lack t-
cell
receptors (tcrs). tcrs from a donor can be recognised by the patient?s
immune
system as ?foreign?, resulting in a ?rejection? called graft versus host disease (gvhd). consequently, nk
cell
s
represent an opportunity for ?off-the-shelf? allogeneic approach versus an autologous approach. ? they have the ability to recruit and prime t-
cell
s
, generating a broad adaptive
immune
response as well. nkarta is developing a best-in-class nk
cell
engineering platform that will allow for either allogeneic or autologous therapies. rgenix ? stopping tumour escape mechanisms rgenix is developing first-in-class drugs targeting key pathways in cancer progression. the company?s lead programme is a small molecule that blocks the ability of tumours to evade the
immune
system. fig. 3 adoptive
cell
therapy adoptive
cell
immunotherapy typically involves at least four basic steps. 1) peripheral blood mononuclear
cell
s
(pbmcs) are isolated from the patient or donor; 2) these
cell
s
are manipulated through various means to poten- tiate activity; 3) modified
cell
s
are expanded ex vivo; 4) the modified
cell
s
are introduced into the patient. continued from p. 33 34 novo a/s 2016
tumour-antigen-immune-35.html
