Getting to Know Your T Cells
If you've been on chemotherapy, you probably already know how it targets quickly dividing cells to kill cancer. But if your cancer is advanced, eventually chemo could stop working. Learning that your cancer is still growing can be hard to hear, but it just means that it's time to move on to the next stage of your treatment. That could involve immunotherapy, a newer lung cancer treatment that boosts your body's immune army of cancer fighters to help them target the cancer more effectively. The soldiers of this army are called T cells.
What Are T Cells?
T cells are a type of white blood cell—but not just any white blood cell. They're "trained" to spot the difference between your own cells and intruders like viruses and bacteria. When they detect these foreign invaders, T cells lock onto proteins called receptors on the germ's surface like a key fitting into a lock and mark it for destruction. These immune cells are also supposed to protect you from cancer, but sometimes "T cells can be asleep at the wheel," says Ben Creelan, M.D., associate member in thoracic oncology at Moffitt Cancer Center in Tampa. "Just like with security or law enforcement, they're not there working 100% of the time."
How Do T Cells Fight NSCLC?
New cell-based therapies harness your own T cells' natural cancer-fighting ability against NSCLC. But first, they give these cells a little boost. "They have to be primed to recognize the cancer, then to be activated, and then to proliferate [multiply] so that there are enough of them to kill the cancer," says Vincent Lam, M.D., assistant professor of oncology at Johns Hopkins in Baltimore. Cellular therapies use a few different approaches to get your T cells ready and enhance your immune system's natural cancer-killing response.
Releasing the Brakes on Your Immune System
One type of immunotherapy that's already being used to treat NSCLC is checkpoint inhibitors. Your T cells have proteins called "checkpoints" on their surface, which essentially put the brakes on them to prevent them from attacking your healthy cells. Cancer cells sometimes sneak behind these checkpoints to avoid being attacked. New immunotherapy drugs like nivolumab (Opdivo) and pembrolizumab (Keytruda) "release the brakes on the T cell," Dr. Lam says. "The medicine itself doesn't kill anything. It just amplifies, enhances, and turns on your immune response, and then your immune system goes and kills the cancer."
Making Your T Cells Better Cancer Fighters
Another group of treatments, called adoptive cell therapies, takes advantage of the T cell's natural cancer-fighting ability, but boosts it even more. Basically, doctors change your T cells in ways that make them more efficient at targeting your cancer. "There are multiple strategies to try to enhance this cancer-fighting response," Dr. Lam says. Three of them are tumor-infiltrating lymphocyte (TIL) therapy, engineered T cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T cell therapy.
Boosting Your Natural Cancer Killers With TIL
Some of your T cells have already figured out how to recognize your tumor and have started to attack it. That's the good news. The bad news is, there may not be enough of these cells to fully conquer your cancer, and they may not be very efficient. That's where TIL therapy comes in. Doctors pull some of the T cells from your tumor, activate them, and then multiply them into numbers large enough to make a much bigger dent in your cancer.
Genetically Modified Cells
TCR therapy takes T cells that aren't quite as good at finding and attacking your tumor, and then transforms them into more efficient cancer fighters. Doctors modify the genes in your T cells, adding a new receptor on their surface to help them latch onto the cancer cells. "You're inserting a specific…gene sequence that allows the T cell to target a protein that's specific to your tumor," Dr. Creelan says. TCR therapy works against many protein targets, which makes it highly customizable to each person's cancer.
Seek and Destroy
The adoptive cell therapy that's the furthest along in studies is CAR T-cell therapy. For this treatment, your doctor takes out some of your T cells and sends them to a lab, where they're genetically modified to produce proteins on their surface called chimeric antigen receptors. Then, those modified CAR T cells are multiplied into the millions. Once inside your body, the receptors on their surface seek out a target protein on the cancer cells and kill those cells.
Experts call these T-cell-based treatments "living drugs" because they remember your cancer, and they keep targeting it, long after you get them. "One of the hallmarks of cell therapy is the potential for cells in your body that can continuously patrol and prevent the tumor from recurring," Dr. Creelan says. Unlike the effects of chemotherapy, which last in your body for 2 to 3 days, memory T cells have the potential to keep working for many years. "Just like memory to COVID-19 or memory to chickenpox, this should last your entire lifetime," he adds.
What About Side Effects?
Chemotherapy has pretty predictable side effects, including nausea, tiredness, and hair loss, because it kills both cancer cells and healthy ones. Although people usually tolerate T-cell therapies pretty well, Dr. Lam says, their side effects are different. "When you're on immunotherapies, your immune system may become overactive and then it starts attacking normal tissues," he adds. Some of its rarer but more severe side effects end in "itis," which means inflammation—of organs like the kidney (nephritis), the heart (myocarditis), or the liver (hepatitis). "We advise our patients just to stay vigilant," he adds.
The Advantages of T Cell Therapy
One thing these new treatments can do is buy you time, a precious resource when you have lung cancer. "With chemotherapy, we almost never see a durable remission in non-small cell lung cancer," Dr. Creelan says. "We're talking about years with immune therapy." New treatments like the checkpoint inhibitors are part of the reason why deaths from NSCLC have dropped by about 6% a year since 2013. For people with stage 4 NSCLC, immune therapies offer "unprecedented survival," Dr. Lam says.
Checkpoint inhibitors are available right now to treat NSCLC, but adoptive cell therapies for this cancer are still experimental. "We're expecting that cell therapy will be available for metastatic melanoma and cervical cancer by the end of the year, and hopefully, it will be available for lung cancer within a couple of years," Dr. Creelan says. For now, you can try one of these treatments by enrolling in a clinical trial. Ask the doctor who treats your cancer if one of these studies might be right for you.
Chemo and NSCLC: American Cancer Society. (n.d.) “Chemotherapy for Non-Small Cell Lung Cancer.” https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/chemotherapy.html
Adoptive Cell Therapy: Cancer Research Institute. (n.d.) “How Cellular Immunotherapies Are Changing the Outlook for Cancer Patients.” https://www.cancerresearch.org/en-us/immunotherapy/treatment-types/adoptive-cell-therapy
CAR-T Cell Therapy: UCLA Health. (2018.) “CAR-T Cell Therapy: This is Your Brain on Living Drugs.” https://www.uclahealth.org/neurology/car-t-cell-therapy-this-is-your-brain-on-living-drugs
Lung Cancer Deaths Stat: National Institutes of Health. (2020.) “Treatments linked to drop in lung cancer deaths.” https://www.nih.gov/news-events/nih-research-matters/treatments-linked-drop-lung-cancer-deaths