How are NK cells being used in anti-myeloma therapy?

How are natural killer cells being used in anti myeloma therapy. There are a lot of ways that NK cells are being developed to try to treat blood cancers, in particular multiple myeloma. So one is just general non engineered NK cells and this has been looked at in patients with leukemia as well. So even just given infusion of NK cells, whether you get them from a healthy donor or from cord blood and see if they have anti-tumor effects. 

And so this, this work has been done by a very variety of different investigators. And what we know from that work is that the NKs are safe and sometimes and especially in leukemia can induce remissions which then allow patients to get other therapies so they buy time. Another way that NK cells can be used is to have them engineered, for example, in making an NK car. 

This allows the NK cells to be specific against the myeloma protein and really directly toxic to the myeloma cells. So it's a little bit more complicated to make those, but generally something that we think about as potential off the shelf car therapy. A third way that you can use NK cells is develop them to be really towards the tumor.

So we have this and g2d possible cell and that can really go towards tumor cells. Trying to look at the actual proteins that generally tumor cells express. You can also change the NK cells or engineer them to be more active with an antibody so some NK cells can be engineered for their little protein on the surface called CD 16 to be better to work with daratumumab.

And finally, there's a group of NK cells called Memory NK cells which are being developed, and these actually are a naturally occurring population of NK cells in certain people, healthy donors who may have been exposed just in regular life to cytomegalovirus, which is a very common virus that many of us are exposed to. And for people who have been exposed to that, they actually have a slightly higher number of these quote unquote memory NK cells which signal very well with antibodies.

And so if you take those cells, grow them in a dish and make serial products, you could actually infuse them with something like daratumumab to make them more effective in conjunction with that antibody or any antibody that might be effective against myeloma. Do we have clinical trials for natural killer cells in multiple myeloma? Yes, we do. Early results were not that encouraging.

So the field of natural killer cell was lagging behind other types of white cells like T cells. However, there is new there are new research going on about different clinical trials, testing the efficacy of natural killers. For example, after stem cell transplant, patients can get, you know, infused with natural killer cells the same way similar to the T cells, the car T cells, and, you know, check for efficacy for natural killers against multiple myeloma.

I think natural killer cells are very powerful cells. They we just need to to learn how to unleash their power against multiple myeloma to harvest most of the benefits out of that. For the time being, it's still early. It's lagging behind chimeric T cells. The CAR-Ts But it's coming and and it's it's it's a promising, you know, biology behind the natural killer cells and the way they fight cancer.

One example we have with treatment with elotuzumab, it's yes, it activates the natural killer cells to go after multiple myeloma Elotuzumab by itself did not show much of efficacy against multiple myeloma. But then we learned that, you know, when you combine elotuzumab with Pomalidomide or with lenalidomide, we get better results than Pomalidomide or lenalidomide respectively alone.

So, yes, elotuzumab added to the myeloma armamentarium. It's an important drug for multiple myeloma. It's good to have an option there, but we still can improve on that and get more of the natural killer cells. Well, that's very much under study. The natural killer cells are also being studied as potential treatments of adoptive cells therapy for myeloma.

In this case, the you're isolating natural killer cells rather than T cells. And then the natural killer cells go through a gene modification process using viruses and other things that deliver the the car to the car molecule, to the NK cells. And then the cells are, you know, expanded and then prepared for infusion back to the patient.

But they do seem to be potentially different in that they don't seem to be associated as much with the cytokine release syndrome and probably the neurologic toxicity because they, they release, you know, different chemicals, different cytokines and they result in the production of different cytokines. So they may have a different, maybe even a less significant side effect profile.

They also because natural killer cells are, you know, have have some less specific some ability to interact with tumor cells in a less specific and targeted way. It's possible that they may, you know, have maybe a wider spectrum of activity or killing than than the T cells, which tend to be more targeted to specific, markers or epitopes on the on the cells cell surface.

Yeah, you could, you could engineer them to go after the same antigens that the T cells can, but the function of the functional properties of the cells are different. And may that may be advantageous in that there may be, you know, less side effects and there may be different, they may have a, maybe a potentially greater ability to, to kill myeloma cells even through some of the nonspecific, ways that the natural killer cells do.