{"id":2271,"date":"2022-09-21T09:41:04","date_gmt":"2022-09-21T09:41:04","guid":{"rendered":"https:\/\/preprod.treefrog.fr\/stemcelljungle\/?p=2271"},"modified":"2023-02-14T09:44:28","modified_gmt":"2023-02-14T09:44:28","slug":"the-promise-of-nk-cells-in-immuno-oncology-mode-of-action-comparison-with-ts-safety-profile-neil-sheppard-stem-cell-jungle","status":"publish","type":"post","link":"https:\/\/preprod.treefrog.fr\/stemcelljungle\/the-promise-of-nk-cells-in-immuno-oncology-mode-of-action-comparison-with-ts-safety-profile-neil-sheppard-stem-cell-jungle\/","title":{"rendered":"The promise of NK cells in immuno-oncology, Mode of Action, Comparison with Ts, Safety profile | Neil Sheppard | Stem Cell Jungle"},"content":{"rendered":"\t\t
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Neil Sheppard, D.Phil, Adjunct Associate Professor in the Department of Pathology & Laboratory Medicine, and Head of the T Cell Engineering Lab (TCEL), at the Center for Cellular Immunotherapies (CCI) at the University of Pennsylvania has a 20-year experience in the field of immunotherapies and vaccines. Why is there so much interest in NK cell therapies within the biotech industry ? What is there mode of action in comparison to T cells ? What’s their safety profile ?<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Even in the last six\/seven years, there’s been an absolute proliferation of biotech companies working predominantly on NK cells and it shows that there’s a lot of capital chasing these ideas they are very promising. So you’re quite right I mean, an NK cell, part of the job of an NK cell, is to recognize transformed cells, usually at an early stage, and shut them down. And primary NK deficiency is actually incredibly rare. So we only have like, medical histories of about fewer than 20 patients who have no NK-cells but the rest\u00a0of their immune system works. And those people – that it’s not a bubble boy disease – these people do\u00a0survive generally, survive childhood. But they often die in early adulthood. And they die really for a couple of reasons. One of them is the uncontrolled viral infections typically with\u00a0the herpes virus family that have become very good at avoiding T cells by down-regulating MHC. So if\u00a0the cell doesn’t express MHC the T cell can never see it. So NK cells and what they’ve evolved to\u00a0recognize cells on which MHC has been tampered with and lowered so they’re very good at combating\u00a0these cells. The other cause of death in these patients is cancer. So by the time cancer has\u00a0developed, it’s already escaped the NK of the individual patient but our NKs play a really\u00a0important role in stopping cancer emerging in the first place. So NKs are a cell type where it’s\u00a0actually probably much better, it’s definitely much better, to use them from an allogeneic source. Because NK cells, one of the ways they decide whether to kill or not is if they recognize their own MHC. They will tend not to kill. And if you take them from an allogeneic donor, its\u00a0KIRs isn’t matching (killer inhibitory receptor).<\/p>

If its killer inhibitory receptor is mismatched, it\u00a0doesn’t have that negative signal. So it’s more likely to kill a tumor cell. The other really cool thing about them is that unlike T-cells,<\/p>

they don’t mediate GvHD. So if you’re using them in the allogeneic setting, you don’t need to match them to the donor. You don’t need to\u00a0delete the TCR. There isn’t one. They don’t do GvHD.<\/p>

And they don’t seem to cause neurotoxicity or\u00a0cytokine release syndrome. So they seem to be very safe and that will be important because one of the\u00a0main cost drivers of say CAR-19 therapies that exist today is the chance of severe side effects that\u00a0could cause hospitalization. The need to receive the therapy in a hospital setting and be checked\u00a0for immediate reactions before you are discharged.<\/p>

With the NKs, they seem to be so safe that if this\u00a0bears up in late phase trials, they could just be simply given in an infusion center, just like a\u00a0monoclonal antibody for example. So that’s very promising. They can because they recognize tumors\u00a0directly. You don’t have to put a CAR in them. But they do work even better if you do. But that means\u00a0that they may be able to prevent antigen escape rather than T cells. Because once\u00a0a tumor cell has lost the antigen, the T cell can’t see it anymore. NK cells may well still be\u00a0able to see it through their other mechanisms.<\/p>

So that’s all really exciting. Then we definitely\u00a0should be using them in the allo(geneic) source.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Neil Sheppard, D.Phil, Adjunct Associate Professor in the Department of Pathology & Laboratory Medicine, and Head of the T Cell Engineering Lab (TCEL), at the Center for Cellular Immunotherapies (CCI) at the University of Pennsylvania has a 20-year experience in the field of immunotherapies and vaccines. Why is there so much interest in NK cell therapies within the biotech industry ? What is there mode of action in comparison to T cells ? 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