Nanotubes improve CAR-Ts for cancer therapy

The Problem

Cancer treatment is rapidly changing for the first time in decades. Recently, CAR-T cell therapies have taken the clinic by storm due to their effectiveness against previously hard to treat cancers. Namely blood and immune cell cancers called leukemias and lymphomas.

CAR-T cells are the patients own T cells, a type of immune cell, that are engineered to target cancer-specific markers. You can think of them as immune cells with a homing beacon directly to the cancer.

But, like many other cell therapies, producing CAR-T cells is expensive and inefficient. The process of making the cells seems simple:

1. Get T cells from patient.

2. Deliver genes to them so they produce a CAR to find the cancer.

3. Give CAR-T cells back to patient.

Unfortunately step 2 is, uh, pretty difficult. Getting foreign DNA material inside of a living cell is hard. As you can imagine, cells don’t like taking in random things in their surroundings. If they did, things like viruses and bacteria would be even worse than they are.

To overcome the T cells lack of appetite, scientists use various tricks including exposing the cells to electricity (referred to as electroporation). This causes the outside of the cells, called the cell membrane, to temporarily open up and let the CAR DNA in. Once in, the electricity is stopped and the cell membrane goes back to normal.

One problems: most of the surviving cells didn’t actually get any of the CAR DNA.

In short, it’s super inefficient. Zapping the cells lets us get some CAR DNA in, but not well. (It’s important to keep in mind that this is good enough to make life-saving therapies for patients, but that doesn’t mean it’s ideal).

Like many things made by scientists, CAR-T cells were first made at the lab scale. Efficiency isn’t the name of the game in the lab, cool new discoveries are. Since they’ve made their name in the clinic and proven their worth, improving the production of CAR-T cells has been an intense focus for both academic and industrial research labs.

The Solution - Nanotubes

Today’s paper focused on improving the efficiency of CAR-T production by using nanotubes to delivery electricity on a much more controllable and precise scale than the typical methods.

Cells are placed on top of these electrically conductive nanotubes. The nanotubes put force on the cell membrane to open it while simultaneously delivering an electric current, leading to efficient but not harmful delivery of the DNA cargo.

Usually, using electricity to deliver DNA takes 100s of volts of electricity, which is expensive, dangerous, and harmful to the cells. The nanotube approach brings this down to only 10 volts, which is safer and easier to achieve.

The nanotubes beat out the conventional bulk electricity approach by a wide margin. Using the typical approach, the scientists achieved about a 16% success rate getting the T cells to express the CARs (BEP in the graph below) . With the nanotube approach, this shot up to 43% (ENI -10V).

New techniques like this are critical for expanding CAR-T cell’s clinical impact. Producing them in safer, more efficient ways will make them less expensive and more widely adopted. Hopefully we’ll see more materials-based techniques hitting clinical problems!

See you next week for more science,

Neil

If you liked this post and want to keep getting cool science delivered to you, sign up for free: