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Treatment and the treatment process

Immunotherapy and CAR-T

Every day, our immune system finds and destroys abnormal cells in the body. Leukemia cells, however, are often able to “hide” from it. Immunotherapy is treatment that helps the immune system recognise these cells again and attack them. This topic explains in plain language monoclonal antibodies, medicines that “link” T cells to leukemia, and CAR-T cell therapy.

Last updated: ~5 min read
A large translucent violet cell on a dark navy background; many small glowing Y-shaped antibodies are attached to its surface.
Figure 1.Concept: antibodies attach to markers on the surface of a leukemia cell.

01Short answer

Immunotherapy is treatment that uses the power of the immune system to fight leukemia. Its main types in leukemia are: monoclonal antibodies that attach to a marker on the leukemia cell surface; antibodies that carry a medicine (antibody–drug conjugates); bispecific antibodies that link a T lymphocyte to a leukemia cell; and CAR-T therapy, in which a person’s own T cells are modified in the laboratory. These treatments are used especially in B-cell ALL and CLL. Because they can cause particular side effects, such as cytokine release syndrome, they are given in experienced centres.

02Simple explanation

Every cell carries protein “flags” on its surface, such as CD19, CD20, CD22 or CD33. Immunotherapy uses these flags as an address: the medicine finds exactly the cell that carries the flag.

A monoclonal antibody is a protein made in the laboratory that attaches to a particular flag. It “tags” the leukemia cell for the immune system or harms it directly.

Some antibodies carry a powerful medicine with them. This is like an addressed parcel: the medicine is delivered only inside the target cell.

A bispecific antibody is like a bridge with two hands: with one it holds a T lymphocyte, with the other a leukemia cell, and it brings them together. The T cell then destroys the leukemia cell.

In CAR-T therapy, a person’s own T cells are collected from the blood, given a new “sensor” that recognises leukemia in the laboratory, and returned. These cells multiply in the body and work as a “living medicine”.

03Scientific explanation

Main types: according to NCI, immunotherapy is treatment that helps the immune system fight cancer; it includes monoclonal antibodies, T-cell transfer therapy (including CAR-T) and other types. According to the American Cancer Society, antibodies against CD20 (rituximab, obinutuzumab) are used in CLL; in ALL, blinatumomab (a bispecific antibody that binds CD19 and CD3) and inotuzumab ozogamicin (an antibody–drug conjugate aimed at CD22) are used. In AML, gemtuzumab ozogamicin, aimed at CD33, is used.

Trial results: in the 2016 INO-VATE trial, inotuzumab ozogamicin gave higher remission rates than standard chemotherapy in relapsed or refractory ALL. In the 2017 TOWER trial, blinatumomab lengthened overall survival compared with chemotherapy in the same group.

CAR-T: according to NCI, CAR T cells are made from a person’s own T cells; in the laboratory they are given a chimeric antigen receptor (CAR) that recognises a particular protein on the surface of cancer cells. In the 2018 ELIANA trial, the CD19-directed product tisagenlecleucel produced remission within three months in about 8 in 10 children and young adults with relapsed or refractory B-cell ALL.

Special side effects: the 2019 ASTCT consensus standardised the grading of cytokine release syndrome (fever, low blood pressure, need for oxygen) and immune effector cell-associated neurotoxicity syndrome (ICANS: confusion, difficulty speaking, seizures). According to the American Cancer Society, after CAR-T people need to stay near the treatment centre for several weeks and not drive for a period of time (US guidance).

04What happens in the body?

CAR-T step by step

First, T cells are collected from the blood by a procedure called leukapheresis. They are sent to a laboratory, where over several weeks they are modified and multiplied; during this time “bridging” treatment may be given to keep the leukemia under control. A few days before the infusion, mild chemotherapy (lymphodepletion) is given to prepare the immune system. The CAR-T cells are then usually given back as a single drip.

How monoclonal antibodies are given

Antibodies are usually given as a drip into a vein, and sometimes under the skin. Reactions such as fever, chills, rash or breathlessness are more common during the first infusion, so medicines are given beforehand and the infusion is started slowly. Before CD20 antibodies, hepatitis B infection is checked, because it can flare up again.

Two cells on a dark navy background: a small blue T cell on the left and a large violet cell on the right, joined by a thin glowing golden bridge.
Figure 2.A bispecific antibody links a T cell to a leukemia cell like a bridge.

How is blinatumomab given?

Blinatumomab stays in the body only briefly, so it is usually given as a continuous infusion into a vein over several weeks. A person can be at home with a small portable pump, but in the first days they are often observed in hospital because of the risk of cytokine release syndrome and neurological symptoms. Catheter care is especially important during this time.

Several blue cells with glowing sensors on their surfaces surround violet cells on a dark navy background; soft light glows where they touch.
Figure 3.CAR-T cells find and attack leukemia cells.

What to watch for after CAR-T

Tell your team straight away about fever, dizziness, shortness of breath, confusion, difficulty speaking, drowsiness, shaking or seizures. CAR-T can also destroy normal B cells, which lowers antibody levels; sometimes immunoglobulin infusions are needed. Follow your team’s advice on preventing infection and on vaccines.

A transplant is immunotherapy too

In an allogeneic stem cell transplant, the donor’s immune cells can attack remaining leukemia cells; this is called the “graft-versus-leukemia” effect. At relapse, extra donor lymphocytes are sometimes given as well. So a transplant is also a treatment that relies on the power of the immune system.

05How is CAR-T therapy given?

Four steps from your own cells to a “living medicine”.

Collection — T cells are taken from the blood by leukapheresis.1CollectionT cells are taken from the blood by leukapheresis.
Modification — In the laboratory, T cells are given the CAR sensor.2ModificationIn the laboratory, T cells are given the CAR sensor.
Infusion — After mild chemotherapy the cells are given back.3InfusionAfter mild chemotherapy the cells are given back.
Attack — CAR-T cells find and destroy leukemia cells.4AttackCAR-T cells find and destroy leukemia cells.
Target markerOften CD19 (in B-cell leukemias).
Living medicineThe cells multiply and persist in the body.
Close monitoringFor cytokine syndrome and neurological symptoms.

06Types of immunotherapy in leukemia (simplified)

TypeHow it worksExamples and use
Monoclonal antibodyAttaches to a marker on the leukemia cell and tags itRituximab, obinutuzumab (CD20) in CLL
Antibody–drug conjugateThe antibody delivers a powerful medicine straight into the cellInotuzumab ozogamicin (CD22) in ALL; gemtuzumab ozogamicin (CD33) in AML
Bispecific antibodyLinks a T cell to a leukemia cellBlinatumomab (CD19 and CD3) in B-cell ALL
CAR-T cell therapyModified own T cells recognise and destroy leukemiaCD19-directed products in B-cell ALL, and in some cases CLL
Allogeneic transplantDonor immune cells attack the leukemiaHigh-risk or relapsed leukemias

* Approved medicines and uses differ from country to country. Whether immunotherapy suits you is decided only by your hematology team.

07Key terms

Immunotherapy
Treatment that helps the immune system fight leukemia.
Monoclonal antibody
A laboratory-made protein that attaches to a specific target.
Antibody–drug conjugate
An antibody that carries a powerful medicine.
Bispecific antibody
An antibody that binds two different targets at once.
CAR-T
A person’s own T cells given a receptor that recognises leukemia.
Leukapheresis
Collecting certain white cells from the blood with a machine.
Lymphodepletion
Mild chemotherapy before CAR-T that lowers lymphocyte numbers.
Cytokine release syndrome
Fever and low blood pressure caused by strong immune cell activation.
ICANS
Neurological side effects linked to immune effector cells.
B-cell aplasia
Loss of normal B cells, which lowers antibody levels.

08Key points

  • Immunotherapy helps the immune system recognise leukemia.
  • The target is often a CD marker on the cell surface.
  • Monoclonal antibodies are used in CLL and ALL.
  • A bispecific antibody links a T cell to leukemia.
  • CAR-T uses a person’s own modified T cells.
  • Cytokine syndrome and neurological symptoms are monitored.
  • After CAR-T you need to stay near the centre for a while.
  • Only your hematology team decides whether it suits you.

09Frequently asked questions

Is CAR-T suitable for everyone?

No. CAR-T is approved for certain types of leukemia and situations, such as relapsed or refractory B-cell ALL. Whether it is an option depends on the leukemia type, previous treatment and general health.

How long does it take to make CAR-T cells?

Usually several weeks pass between collecting the cells and giving them back. During this time other treatment may be given to keep the leukemia under control.

Is cytokine release syndrome dangerous?

It can range from mild to severe. Teams are prepared to recognise and treat it early. That is why it is so important to report any fever or new symptom straight away.

Does immunotherapy replace chemotherapy?

In some cases it partly replaces it or is given alongside it. Many treatment plans use both at different stages. Your hematologist decides the order.

Can I have vaccines after CAR-T?

Some vaccines are recommended after a certain time, while live vaccines usually need to be avoided. Always agree your vaccination plan with your team.

Does immunotherapy cause hair loss?

Monoclonal antibodies and CAR-T themselves do not usually cause hair loss. But chemotherapy given alongside them can.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is immunotherapy or CAR-T being considered for me?

  2. What are the main risks of this treatment?

  3. Which signs after treatment should I report straight away?

  4. Where and under what conditions is this treatment available?

My questions

12Sources

  1. National Cancer Institute (NCI). Immunotherapy for Cancer
  2. National Cancer Institute (NCI). CAR T Cells: Engineering Immune Cells to Treat Cancer
  3. National Cancer Institute (NCI). T-cell Transfer Therapy
  4. National Cancer Institute (NCI). Monoclonal Antibodies
  5. National Cancer Institute (NCI). Side Effects of Immunotherapy
  6. American Cancer Society. What Is Immunotherapy?
  7. American Cancer Society. CAR T-cell Therapy and Its Side Effects
  8. American Cancer Society. Monoclonal Antibodies and Their Side Effects
  9. American Cancer Society. Immunotherapy for Acute Lymphocytic Leukemia
  10. American Cancer Society. Immunotherapy for CLL
  11. Cancer Research UK. CAR T-cell therapy
  12. New England Journal of Medicine, 2016. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia
  13. New England Journal of Medicine, 2017. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia
  14. New England Journal of Medicine, 2018. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
  15. Biology of Blood and Marrow Transplantation, 2019. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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