TIL therapy: 6 things to know

Adoptive cellular therapy is a form of immunotherapy that uses cells from our immune systems, such as T cells, as a treatment for cancer. The immune cells are usually isolated from a patient, expanded and, in some cases, engineered to enhance their natural abilities to eliminate cancer.

This field has grown significantly in recent years with the FDA approval of chimeric antigen receptor (CAR) T cell therapies for certain patients with blood cancers. CAR T cells are engineered to recognize specific targets on cancer cells.

Tumor-infiltrating lymphocytes (TILs) are an experimental cell therapy being developed for treating solid tumors. To learn more about TIL therapy and MD Anderson’s research, we spoke with Jason Bock, Ph.D., vice president of Therapeutics Discovery and head of Biologics Development.

What is a tumor-infiltrating lymphocyte?

Lymphocytes, or white blood cells, are an important part of the immune system that helps the body fight off infections or eliminate diseased cells. Lymphocytes, made up of T cells and B cells, are constantly patrolling the body to identify cells that shouldn’t be present, including cancer.

As cancers grow, lymphocytes recognize these cells as abnormal and penetrate into the tumor. These are the tumor-infiltrating lymphocytes, or TILs.

Once in the tumor, the TILs begin working to kill cancer cells. Sometimes, they’re prevented from doing that by brakes in the immune system or signals from the tumor that weaken the immune response. Immune checkpoint inhibitors were developed to block some of those brakes and unleash the immune cells to attack cancer.

We also can use the TILs themselves, with some improvements, as a form of cell therapy.

How can these cells be used for cancer therapy?

Because TILs come directly from the tumor, they already recognize many targets on the cancer cells. This makes them a very attractive therapy because we don’t have to do anything to point them toward the tumor.

That’s different from CAR T cells, for example, which must be genetically engineered to recognize one, or maybe two, targets. A group of TILs taken from a patient’s tumor may recognize many unique targets. This offers a real therapeutic advantage because it prevents the tumor from evading our efforts by hiding one target at a time.

To use TILs as a therapy, we must help them overcome the hurdles in the tumor environment and effectively eliminate the cancer. We can do this in two ways:

• expanding the TILs
• engineering them with certain attributes

By expanding the TILs, we can give the patient a much larger army of immune cells that is already trained to recognize and attack that patient’s specific tumor.

Engineering TILs enhances their ability to fight the cancer cells. There are several research projects in this area ongoing at MD Anderson. For example, we can genetically engineer TILs to be resistant to signals coming from the tumor that normally turn off the T cells .

What’s the treatment process for patients who undergo TIL therapy?

Currently, TIL therapies are only available through clinical trials. For patients who enroll in a TIL clinical trial, the process begins with a tumor biopsy. That biopsy is then taken to a clinical laboratory, such as our Cell Therapy Manufacturing Facility,  to isolate the TILs.

Trained experts perform the expansion and engineering in a process that typically takes about a month. We’re working to improve our speed in this area, though, to get therapy to patients more rapidly.

From there, the process is similar to other cell therapy procedures. When the TILs are ready, we give the patient a short-term chemotherapy regimen to prepare the body for the cells. Then, the patient receives the TILs through infusion, just like a typical blood infusion. Once infused, the TILs travel directly to the tumor to begin their work.

Afterward, the patient receives some immune-modulating therapies, such as interleukin 2 (IL-2), to stimulate the TIL activity. A patient will be in the hospital for at least a few days so doctors can monitor for any side effects or reactions to the therapy. TIL therapy is a one-time treatment. 

Are there expected side effects to TIL therapy?

So far, we have not seen any major side effects from the TILs themselves. Most side effects we see come from the chemotherapy regimen or the IL-2, which can be managed.

We are working to engineer TILs that could produce their own immune-stimulatory signal. This would eliminate the need for us to treat the patients with IL-2 and could reduce side effects overall.

Has TIL therapy been successful in treating cancer?

We have been evaluating TIL therapies in clinical studies for years and there are encouraging results in early-phase studies. Most of the studies thus far have treated patients with melanoma, but other indications are now being explored.  

What is interesting is that TILs appear to be a long-lasting therapy. We’ve seen evidence that TILs can be found still patrolling the body several years after infusions, and they can eliminate recurrences before we’ve even detected them on scans.  Some patients can be tumor-free for many years after a single TIL infusion.  

While that is early data, we’re working very hard to understand how that happens so we can maximize benefits for all patients. We’re also working to improve the manufacturing process, which has been a hurdle in the field. Combining MD Anderson’s expertise in TIL therapies with the robust manufacturing capabilities of our cell therapy manufacturing facility, we are hopeful that we can overcome this challenge in the near future.

Why are you excited about the future of TIL therapy?

I believe that TIL therapy offers a promising option for patients with solid tumors. So far, we haven’t seen great success from CAR T or other cell therapies in treating patients with solid tumors. However, by the very nature of TILs, we have years of data demonstrating them to be more successful for these cancer types.

There is a TIL therapy that has completed clinical trials and may be evaluated this year by the Food and Drug Administration, so I am excited to see if perhaps there will be an approved TIL therapy on the horizon.

The great Wayne Gretzky liked to say, “Skate to where the puck will be, not where it is.” I believe TIL therapy is where the puck is going – it is poised for a significant impact in the field of cell therapy. We are proud to be part of bringing those advances to our patients.

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