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Novo Annual Review 2016
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from patient 1 cell infusion 4 cell expansion 3 activate cells 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
cells. a type of adenosine receptor known as a2a is expressed on several cells of the immune system, including t-cells, nk cells, macrophages and dendritic cells. binding of adenosine to the a2a receptor has the effect of limiting the immune cells? 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 cells nkarta therapeutics is focused on developing therapies using natural killer (nk) cells. nkarta?s core capability, developed by scientific founder dario campana, is the consistent expansion and genetic modification of primary nk cells for adoptive cell immunotherapy (for an overview of this process, please see fig. 3). nk cells have an intrinsic ability to distinguish transformed versus normal cells. nk cells are unique based on the following attributes: ? they do not require activation to kill cells that are missing ?self? markers. this is especially important because harmful cells that are missing ?self? markers cannot be detected and destroyed by other immune cells, such as t-cells. ? 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-cells. ? 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 cells represent an opportunity for ?off-the-shelf? allogeneic approach versus an autologous approach. ? they have the ability to recruit and prime t-cells, 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 cells (pbmcs) are isolated from the patient or donor; 2) these cells are manipulated through various means to poten- tiate activity; 3) modified cells are expanded ex vivo; 4) the modified cells are introduced into the patient. continued from p. 33 34 novo a/s 2016
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