Patient-Derived Lymphoma Spheroids

That post title is a lot, but it's the subject of some very cool recent research on Follicular Lymphoma that might be a big help to us someday.

The Blood Cancer Journal just published an article called "Patient-Derived Follicular Lymphoma Spheroids Recapitulate Lymph Node Signaling and Immune Profile Uncovering Galectin-9 as a Novel Immunotherapeutic Target." There's a lot of science in that title, and even more in the article, but as I said, it's very cool research.

The article describes the use of something called a Lymphoma Spheroid. As the "sphere" in the name implies, it's kind of a ball of lymphoma cells plus some other things. And here's why it's important.

Before a cancer treatment can be tried out on people in a phase 1 trial, it needs to go through a whole bunch of "pre-clinical" steps. After a possible treatment is developed (and there's whole bunch of steps to go through with that, but that's another post), the next step is come up with a target for treatment, and then figure out if the new treatment will work on that target. This is usually done "in a test tube," mixing the treatment with some cancer cells.

But it's much more complicated than that. Think about it -- if I put some cancer cells in a test tub and then added some gasoline, the gasoline would almost certainly kill the cancer cells. But that's not helpful -- you wouldn't want to put gasoline into your body. It would kill all of your cells, not just your cancer cells. So you need a treatment that will work on the cancer cells but do minimal damage to healthy cells. That's a little bit more of a challenge.

Even then, it gets complicated. A treatment can work fine in a test tube, but then fail when it's given an actual patient. Why? A big reason is the microenvironment for the cell. This is everything that physically surrounds the cell. And the microenvironment plays a huge role in cancer cells surviving. People (you may have noticed) are not just individual cells; we are complex systems. Change one thing in a person, and you're likely to change a bunch of other things. You bang your toe, and soon your back hurts, because you're walking differently. With a sore back, you don't sleep well. Without sleep, you need more coffee. This makes you jumpy and you can't sit for long. this makes your sore back worse. 

You get the idea. Works the same for cancer cells. You try to kill a cancer cell, and something else gets in the way -- an immune cell, an enzyme, a protein. If it was easy to kill cancer cells, you wouldn't be here reading this.

The idea of a Lymphoma Spheroid is an attempt to deal with this challenge. It's been around for a few years, with some interesting research already being done with it.

Rather than just putting an FL cell in a test tube, the Patient-derived Lymphoma Spheroid attempt to create a 3D model of what's happening in the body -- recreating as best it can the microenvironment that the FL cell exists in. The researchers mixed together a formula with about 60% tumor B cells, and then added about 13% T cells that have the CD4 protein, and another 3% that have CD8. The researchers found that this mix kind of organizes itself into something that resembles what's happening in the patient's body, with the spheroid doing things like producing things like PD1 and CD3 that are already targets for treatments.

Just as important, it's showing that there are new targets for Lymphoma researchers to create treatments for, like CD39, a protein on the surface of the cancer cell. Some other research found that Obinutuzumab and Nivolumab, an anti-PD1 treatment, might be effective. 

The article from this week used Patient-Derived Lymphoma Spheroids to show that a protein called galectin-9 can lessen the effectiveness of Rituxan, and so they are proposing that galectin-9 would be a good target for future treatments. 

The most important thing with all of this is not just the "Lymphoma Spheroid" part of it, but the "Patient-Derived" part. Follicular Lymphoma is heterogeneous -- it shows up in very different ways for different patients. That's why there is no real agreement on what the best way to treat it is. But the Patient-Derived Lymphoma Spheroid takes cells from each patient. In other words, this isn't an attempt to study how FL behaves. It's an attempt to study how your FL behaves. We're all different, so recreating your personal microenvironment should, at least in theory, tell your doctor which treatments are likely to work best for you. that's what "personalized medicine" is all about.

Will this ultimately change things? Hard to say. Lots of cool things turn out to work less effectively than we'd hoped, once they get tested out on a large group of patients. But there's already a growing body of research that is showing some success. Time will tell.

But for me, getting (and sharing) a little bit more insight into the process for developing treatments is also the cool part. I often see (and share) research that is much farther along, and the closer it gets to the doctor's office, the more exciting it is. But there is a whole lot of work that goes into that journey from a test tube in a lab to an intravenous tube in a treatment room, and I like the reminder of that.

More good stuff to come. The ASCO abstracts are due out very soon....