What Are Gene and Cell Therapies?

Lately, gene and cell therapies have been getting a lot of buzz—and for good reason. They hold great promise for treating diseases such as cancer, ALS, multiple sclerosis, sickle cell disease, heart disease, and more.

As the largest hospital-based research system in the country, Mass General Brigham has more than 500 researchers and clinicians dedicated to studying gene and cell therapies, from basic research in the lab to clinical trials that test new therapies in patients. Gene therapy innovator Roger Hajjar, MD, serves as head of the Mass General Brigham Gene and Cell Therapy Institute.

“This is a different class of medicine than we’ve seen in the past, and it constitutes a real paradigm shift,” says Florian Eichler, MD, a Mass General Brigham pediatric neurologist who studies the genetics of nervous system disorders.

“These transformative therapies are allowing us to treat some disorders we never thought we’d be able to treat, and they’re helping us treat others in new ways.”

Because gene and cell therapies are so new and different, many people have questions about them. What, exactly, do these new treatments do? How do they work, and what makes them so special?

Consider this a handbook for gene and cell therapy.

Different types of gene and cell therapies

What is the difference between cell therapy and gene therapy? They aren’t exactly the same, but they are closely related, and they sometimes overlap.

“Gene and cell therapy both belong in the realm of precision medicine,” Dr. Eichler explains. In precision medicine, doctors tailor treatments to a person based on their genes or other unique characteristics. 

Here’s how these treatments work.

What is gene therapy?

Many diseases are caused by mutations (mistakes) in a person’s genes. There might be a typo in the DNA. Or a gene might be missing or repeated. Gene therapy is designed to silence a mistake in the gene or replace the faulty gene with a corrected version.

Usually, doctors use viruses to deliver the healthy, corrected version of the gene into the patient’s body. The idea of infecting someone with a virus on purpose might sound strange. But the virus is altered first so it doesn’t cause any disease symptoms, Dr. Eicher explains. “We’re just using it as a delivery vehicle to drop off the gene cargo.”

Once inside, the healthy gene inserts itself into a patient’s DNA, replacing the faulty version. With the mistake corrected, the gene should begin working properly, eliminating the disease.

One technology, CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9), has forever changed the way researchers study gene therapy. It can add, remove, or alter specific locations of genes faster and more accurately than other gene-editing tools.

Gene therapy for leukodystrophies

Leukodystrophies are a group of rare genetic disorders that affect the central nervous system (CNS), which is made up of your brain and spinal cord. Leukodystrophies damage the white matter of your CNS, slowing down or blocking the signals between nerve cells. This can cause many different symptoms, including trouble with movement, vision, hearing, and thinking. There are more than 50 types of leukodystrophies.

As director of the Leukodystrophy Service, Dr. Eichler and his team care for leukodystrophy patients using a combination of symptom management, accepted treatment options, and emerging therapies and research. Mass General Brigham researchers are advancing natural history studies and gene therapy trials for the leukodystrophies (NCT02851862, NCT02851563 and NCT01896102). Through this novel genetic research and technology, they aim to launch new therapeutics for leukodystrophies.

The Mass General Center for Rare Neurological Diseases (CRND) also aims to eradicate leukodystrophies and other rare disorders of the nervous system by leveraging the power of biological insights towards design and implementation of clinical trials.

What is cell therapy?

In cell therapy, doctors transplant human cells into a patient to replace or repair damaged cells. Not all types of cell therapy are new. Blood transfusions are one common example. Transplants of stem cells from bone marrow have been used for decades to treat leukemia and other diseases.

But scientists are making new breakthroughs in cell therapy. In regenerative medicine, doctors might inject fat or bone marrow cells to help heal joint damage. And many promising treatments blend cell therapy with gene therapy. You can think of them as cell-based gene therapies.

Cells modified to treat disease include:

• T-cells (commercialized as chimeric antigen receptor T cells; CAR-T cells)
• B-cells, natural killer (NK) cells
• Tumor infiltrating lymphocytes (TILs)
• Dendritic cells (DCs)

Cell-based gene therapy

With these treatments, doctors remove cells from a patient. In the lab, experts alter those cells using gene therapy. Doctors then implant the modified cells back into the patient’s body, where they fight disease or give rise to new, healthy cells.

How does sickle cell gene therapy work?

The United States Food and Drug Administration (FDA) has approved two gene therapies for sickle cell disease (SCD), an inherited blood disorders resulting in chronic pain. The therapies — Casgevy and Lyfgenia — use two different cell-based gene therapy techniques to treat SCD.

Each treatment extracts stem cells from the bone marrow of a patient and modifies them with gene editing technology in laboratories miles away. While Casgevy relies on CRISPR to modify genes inside stem cells, Lygenia relies on a harmless virus called a lentiviral vector to deliver genetic material. Both help the stem cells blunt the effects of SCD once returned to the patient’s bone marrow.

Is stem cell therapy the same as gene therapy?

Not necessarily. Stem cells are special because they have the ability to turn into many different cell types. Some types of cell therapy use stem cells, but others don’t.

Take CAR-T cell therapy, for example. In CAR-T cell cancer treatment, doctors draw a patient’s blood and remove the T-cells, a type of immune cell. Scientists modify T-cells in the lab and then doctors return them to the patient’s body. There, the altered cells seek out and attack cancer cells. CAR-T cell therapy has been approved to treat lymphoma and multiple myeloma, and scientists are studying its potential for treating other cancers.

Gene and cell therapy examples

Researchers across Mass General Brigham seek new ways to apply gene and cell therapies, including:

Gene therapies for vision, blindness, and Alzheimer’s disease

Mass Eye and Ear researchers have explored using CRISPR gene-editing technology to target mutations responsible for deafness and blindness. Brigham and Women’s Hospital researchers have also studied whether altering a gene in the brain could help treat familial Alzheimer’s disease.

Cell therapy for cancers

Mass General Cancer Center researchers have reported impressive results from a new approach to CAR-T therapy for glioblastoma. They’ve witnessed dramatic reductions in the size of tumors during a clinical trial.

Cell-based gene therapy for sickle cell disease

The Comprehensive Sickle Cell Disease Treatment Center at Massachusetts General Hospital is one of the first centers in the United States approved to administer Casgevy for sickle cell disease.

Gene and cell therapy for cystic fibrosis

Cystic fibrosis (CF) is a genetic disorder that can be life-threatening, and currently has no cure. It causes cells in the respiratory system and other parts of the body to absorb too much sodium and water. That absorption makes thick mucus in the lungs, pancreas, and other organs.

Mass General Brigham researchers are looking to use the science behind gene and cell therapy for cystic fibrosis to slow, stop, and prevent the condition. They also study the use of stem cell therapy to treat damage caused by cystic fibrosis to the lungs, pancreas, and other organs.

“In our labs and in clinical trials, we’re testing different approaches to treatment,” Lael Yonker, MD, a Mass General Brigham pediatric pulmonologist. Dr. Yonker cares for patients at Mass General for Children and is co-director of the Cystic Fibrosis Center. “These trials give people with cystic fibrosis the opportunity to access potential new therapies before they’re widely available.”

Scientists are also researching advanced imaging techniques, which will help doctors understand and create treatments for airway inflammation as well as treatments for people who develop diabetes because of cystic fibrosis.

“Treatment for cystic fibrosis has come a long way in recent years. More and more people with the condition live longer, better lives than ever before,” says Dr. Yonker. “But that’s not enough. We want a cure — gene and cell therapy may hold the key.”

How many gene and cell therapies are FDA-approved?

To date, the FDA has approved more than 30 gene and cell therapies, including Casgevy. But, Dr. Eichler says, researchers are studying thousands more, so that number is likely to grow quickly.

“We’re going to see a huge surge in these treatments,” he predicts.

Many of those approved therapies are offering hope for people with diseases that, until now, have been difficult or impossible to treat.

“All of a sudden, we’re able to address rare diseases that we’ve never been able to treat before,” Dr. Eichler says. More than 7,000 rare diseases are thought to be caused by a mistake in a single gene, he adds. Gene and cell therapy offer an opportunity to fix those genetic errors.

Researchers at Mass General Brigham are leading that effort. “In the past 2 years, the number of gene therapy trials at our hospital has more than doubled, and we expect a lot more growth to come,” Dr. Eichler says. “There are tremendous opportunities to develop new treatments.”