T cell receptor (TCR) therapy is a new type of treatment that uses your own immune cells to fight cancer. It is a promising therapy for some types of cancer, including soft tissue sarcoma.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) are studying TCR therapy in clinical trials, also known as research studies. They hope to learn the best way to use this treatment and who it may help.

What is TCR therapy and how does it work?

TCR therapy is known as an engineered cell therapy. It uses T cells, a kind of white blood cell. T cells are an important part of your immune system. They help your body fight infections and diseases, including cancer.

With this treatment, your own T cells are collected from your blood. They’re changed in a lab to make them able to recognize cancer cells.

After they are changed, the cells are then put back into the bloodstream. This lets them travel throughout your body to find and eliminate tumor cells. 

How is TCR therapy different from CAR T therapy?

TCR therapy is similar to chimeric antigen receptor (CAR) T cell therapy. They’re both therapies that use a person’s own immune cells. CAR T therapy has been approved for treating some blood cancers since 2017.

With both treatments, your T cells are removed, modified (changed), and then put back into your body. The T cells can now recognize a type of protein carried by tumor cells, known as an antigen. The antigen acts as a marker for the immune system.

However, TCR therapy may work better than CAR T therapy for certain kinds of cancer, especially solid tumors.

CAR T therapy helps T cells spot markers on the outside of cancer cells. A unique feature of TCR therapy is that it can identify markers hiding inside cancer cells.

It’s important to be able to find markers inside cells. Many proteins related to cancer are inside cells, not on the cells’ surface. Because TCR therapy can spot markers inside cells, it can recognize more targets in cancer cells.

What is HLA and why is it important for TCR therapy?

TCR therapy uses an extra tool to see inside cells. This tool is called the human leukocyte (LUKE-oh-site) antigen system. A human leukocyte antigen (HLA) is a type of molecule on the surface of most cells. In TCR treatments, the HLA acts like a basket and carries degraded pieces of proteins made inside a cell to be displayed on the outside surface of the cell. This allows a T cell to see if the proteins made inside a cell are normal or abnormal.

HLA markers are proteins that are found on most cells in your body. HLA markers are a way for your immune system to tell which cells belong in your body and which ones do not. Your immune system knows which pattern of HLA markers is normal for your body. If it finds a cell that has a different pattern of markers, it will attack and kill the cell.

People do not all have the same patterns of markers. There are thousands of different HLA types. They are inherited (passed from parents to their child). However, some HLA types are more common than others.

Because people have different patterns of HLA markers, it’s important to find out the HLA type before certain types of medical procedures. These include TCR therapy and blood stem cell (bone marrow) transplants.

For TCR therapy to work, a patient must have the correct HLA type. This is commonly determined through a blood test.

What kinds of cancers can TCR therapy treat?

The U.S. Food and Drug Administration (FDA) approved TCR therapies to treat a rare soft tissue cancer called synovial sarcoma and a rare melanoma called uveal (eye) melanoma. MSK has clinical trials to study if TCR therapy can treat other types of cancers. Researchers believe TCR therapy may one day prove to be a good treatment for many types of solid tumors. They are also studying this approach for certain blood cancers, including leukemia and myelodysplastic syndrome (MDS).

Who is eligible for TCR therapy?

Most often, we recommend TCR therapy if chemotherapy has not worked well and the disease has returned. We may also recommend it if you’ve developed resistance to other treatments.

For TCR therapy to work, it must match the cancer cell marker and the HLA type. Your medical team can do tests to find out if your tumor carries the marker and if your body expresses the correct HLA type.

What is it like to get TCR therapy?

The first step of TCR therapy is to collect the T cells from the blood. The process is called apheresis (a-feh-REE-sis). It is similar to donating platelets. Your blood may be removed through a vein in your arm or through a port. The T cells are filtered out, and the rest of your blood is put back into your body.

The T cells will be taken to the lab. They’ll be modified to carry the TCR gene, which enables immune cells to recognize the markers in your tumor. The cells will then be grown in the lab so there will be many more of them. This process will take a few weeks.

Once the cells have grown successfully, you’ll have chemotherapy. This treatment gets your body ready for the TCR therapy. Chemotherapy improves the chances the TCR-modified immune cells will survive and multiply when they’re put back into your body.

During treatment, the cells will be infused (put back) into your bloodstream through a port in your chest. The cells will then circulate (move) throughout your body and hunt down more tumors.

You may be given more drugs to stimulate your immune system after the TCR infusion, including immune-stimulating hormones. They can help the cells to work even better.

What are the side effects of TCR therapy?

You must stay in the hospital for at least 1 to 2 weeks to get TCR therapy. The chemotherapy may weaken your immune system and make it easier for you to get infections.

TCR therapy also has other side effects. Some of them are like the ones people have after CAR T therapy. Others are caused by the drugs used to stimulate your immune system.

Side effects of TCR therapy can include:

• High fevers and chills.
• Nausea (feeling like throwing up) and loss of appetite (not feeling like eating).
• Headaches, dizziness, and other issues that affect the nervous system.
• Feeling very tired and weak.
• Low blood counts.
• A buildup of fluids in your body, which can put stress on your heart and lungs.

MSK has been treating people with different forms of cellular therapy for many years. We have medical experts from many areas who have experience in safely managing these side effects.