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What is Car-t therapy?

Car-T is a revolutionary, highly specialized and individualized treatment for leukemia, lymphoma and multiple myeloma, with clinical testing for other forms of cancer currently underway. Available at a limited number of cancer centers worldwide, we are pleased to offer Car-T therapy to patients from around the globe at Sheba Medical Center’s Hemato-Oncology Department.

Car-T therapy uses the patient’s white blood cells, which are genetically reprogrammed to kill cancer cells, enabling many patients who did not respond to other treatment methods to achieve remission. At Sheba, we have all the advanced facilities necessary for delivering the therapy from start to finish, including a dedicated laboratory to engineer the T-cells.


How does Car-Twork?

The Car-T process begins with the patient's blood being drawn. Using advanced technologies, white blood cells (WBC), specifically T-cells, an essential part of the immune system, are then separated from the rest of the blood. The WBCs are then transferred to a specialized laboratory, where they are engineered to produce specific chimeric antigen receptors (CARs) on their surface. These Car-T are then reinjected back into the patient’s bloodstream. The new CARs can help the modified white blood cells latch on to an antigen in tumor cells – significantly increasing their ability to effectively hunt down and destroy cancerous cells.

While the modified T-cells grow in our laboratory, the patient receives chemotherapy to suppress their immune system. This creates a more efficient setting for the CAR T-cells to do their job and destroy malignant cells.

A significant benefit of the therapy is that it both stimulates T-cells to fight cancer and triggers their multiplication. Thus, after just one treatment, the cells continue to attack the tumor for months or even years. At Sheba, a global pioneer in the application of the therapy, more than 373 patients have already been treated.

Which types of cancer are targeted by Car-T therapy?

Acute Lymphoblastic Leukemia (ALL)

A form of blood and bone marrow malignancy, Acute Lymphoblastic Leukemia (ALL) is an aggressive and fast-growing disease that can develop at any age (although it is more common in children). In the United States, about 1,000 new ALL cases are diagnosed in adults every year. The disease is characterized by the excessive production of immature lymphocytes called lymphoblasts. These abnormal cells do not function properly and block the production of other types of healthy blood cells, such as red blood cells and platelets.

Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a fast-growing type of leukemia that can develop at any age, although it most frequently affects older adults, with the average age at diagnosis being 65.
AML is a cancer of the blood and bone marrow that occurs when the bone marrow produces immature white blood cells called myeloblasts, which, instead of developing into mature, healthy blood cells, remain undeveloped and multiply, crowding out other healthy cells, such as red blood cells, white blood cells and platelets. In some cases, AML can also spread to other organs, such as the brain, spinal cord, liver or spleen. Without prompt treatment, AML can be life-threatening. Sheba is the first medical center in the world to offer Car-T therapy to AML patients with the t(8;21) translocation as part of a clinical study.

Non-Hodgkin Lymphoma (NHL)

Non-Hodgkin Lymphoma (NHL) is a cancer of the lymphatic system, which transports lymph, a fluid containing disease-fighting white blood cells that circulates through the body, much like blood does.

Non-Hodgkin lymphoma develops in lymphocytes, a type of white blood cells, and is more common in adults than children. The malignancy has several sub-types, the most common of which are diffuse large B-cell lymphoma and follicular lymphoma.

Multiple Myeloma (MM)

Multiple Myeloma (MM) is a form of blood cancer (related to lymphoma and leukemia) originating in the plasma cells, an essential component of your immune system. Plasma cells are a specific type of white blood cells that produce antibodies (immunoglobulins) to find and attack pathogens, thereby fighting infections. MM is relatively uncommon, with the risk of developing this cancer being 1 in 132 in the US.

In MM, the plasma cells multiply abnormally, rapidly crowding out healthy blood cells. Instead of producing antibodies to fight infection, these cells then produce abnormal proteins that accumulate in your bones and blood. The buildup of this abnormal protein (called monoclonal immunoglobulin) damages organs throughout the body. As MM progresses and worsens, the plasma cells spread out from your bone marrow and through your body, causing more damage to other organs.

CAR T-cell therapy is a revolutionary, highly specialized and individualized treatment for leukemia, lymphoma and multiple myeloma.

The Car-T therapy process

Your medical team at Sheba will design a customized Car-T therapy plan to target the specific type of cancer you suffer from. Committed to clear and open communication with every patient, we ensure a lack of ambiguity and tell you exactly what to expect.

Conducting the entire Car-T therapy in-house at Sheba has significant benefits for patient care. With a vein-to-vein time of about 10 days, we have eliminated the need for prolonged bridge therapies necessary to control the disease during the waiting period, which in turn correlates with better patient outcomes. Since there's no need for cryopreservation, the potency and quality of the harvested cells remain intact, enhancing the efficacy of treatment. Additionally, in-house management substantially minimizes the risk of production failures. Altogether, this approach allows for quicker, more efficient and potentially more successful cancer care.

The following outline is a step-by-step description of the Car-T therapy process:

1. Pre-testing

This stage involves determining whether you are a suitable candidate for the treatment. We will perform various tests and screenings to evaluate whether Car-T therapy will be beneficial for you. In addition, Car-T therapy can be considered only after at least one prior line of treatment for lymphoma patients and two lines of treatment for leukemia and multiple myeloma patients.

2. T-cell collection

By using a special machine for apheresis, T-cells will be separated from the rest of your blood cells in a process called leukapheresis, and then frozen.

3. T-cell engineering

The T-cells are then sent to our in-house lab, where they are genetically modified to produce CARs on their surface. CARs are proteins that enable the T-cells to identify particular antigens on the surface of tumor cells, transforming them into CAR T-cells.

4. CAR T-cell multiplication

The specially altered T-cells are grown in the Sheba laboratory until there are millions of them in a process that takes several days.

5. Lymphodepleting chemotherapy

A short course of chemotherapy is administered to deplete existing T-cells prior to the Car-T therapy. The purpose of this chemotherapy cycle is to suppress your immune system slightly so that it does not reject the CAR T-cells once they are infused. Lymphodepleting chemotherapy may cause nausea, fatigue, and low blood counts.

6. CAR T-cell infusion

Shortly after chemotherapy, you will be hospitalized so that we can re-infuse the CAR T-cells into your body. This process is performed in a similar manner to a blood transfusion.

7. Hospitalization and monitoring

While you will only receive a one-time infusion, you may need to stay in the hospital for a few weeks so our doctors can monitor your condition closely and manage any side effects as needed. Typically, it takes about two to three months to recover. Following discharge, should any side effects arise, you may be required to return to the hospital.

8. Follow-up care

After undergoing Car-T therapy, follow-up care plays a vital role in ensuring a patient's wellbeing and monitoring treatment outcomes. Regular and comprehensive check-ups will be scheduled to assess the patient's recovery progress and potential side effects. These follow-up appointments typically involve monitoring blood counts, immune system function, and overall health.

Additionally, healthcare providers will keep a close eye on any signs of recurrence or relapse of the targeted condition. Follow-up care also includes addressing and managing any lingering side effects or complications that may arise post-treatment. Patient education about self-monitoring and recognizing warning signs is often provided to empower them in their recovery journey. The ongoing support and communication with the medical team during follow-up care are essential in promoting the patient's long-term health and quality of life after Car-T therapy. Over the next several years, you will return for blood tests, physical examinations and/or bone marrow biopsies as well as PET or CT scans.

What are the side effects of Car-T therapy?

Generally speaking, most Car-T therapy patients do not experience the typical side effects associated with chemotherapy, such as nausea, vomiting, and hair loss. However, there are risks of other serious side effects. Because Car-T therapy is given as a one-time infusion (and not in sessions, like chemotherapy), most of the possible complications occur within the first one to two weeks after treatment. They are usually temporary and can be resolved with medication. It is crucial to communicate with your medical team at Sheba, so our skilled doctors can help to alleviate and manage your side effects.

Cytokine Release Syndrome

Cytokine Release Syndrome (CRS) is an immune system response that can be a side effect of certain immunotherapies, including Car-T therapy. When CAR T-cells are infused into the body they can trigger the release of cytokines – small proteins that act as signaling molecules in the immune system. In some cases, this immune response can become overly activated, leading to CRS.

Cytokine Release Syndrome Symptoms

  • Fever
  • Flu-like symptoms
  • Elevated heart rate (tachycardia) and breathing (tachypnea) can occur due to the heightened immune response
  • Low blood pressure
  • Rashes
  • Organ dysfunction
  • At Sheba, we closely monitor patients for these symptoms during and after Car-T therapy. Prompt identification and management of CRS can minimize its impact and prevent complications. Our oncology center is equipped to administer specific medications to control CRS and ensure the patient’s safety and successful recovery from immunotherapy.

    Neurological side effects

    Neurological side effects can be another concern following Car-T therapy, and one of the most notable complications is immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS is characterized by symptoms ranging from mild confusion and agitation to more severe manifestations.

    Recognizing and promptly addressing these side effects is crucial to ensuring patient safety and wellbeing during the recovery process. At Sheba, a multidisciplinary team of specialists closely monitors patients for any neurological symptoms. They employ advanced diagnostic tools and protocols to assess the severity of ICANS and determine the most appropriate course of treatment. The focus is not only on treating the immediate side effects but also on providing long-term support and care to optimize the patient’s overall recovery and quality of life.

    Other side effects

    Anemia: Anemia is a common hematological side effect that can occur following Car-T therapy. During the treatment, CAR T-cells may target healthy cells, including red blood cells. As a result, the number of red blood cells in the bloodstream can decrease, leading to anemia. Anemia is characterized by fatigue, weakness, shortness of breath and pale skin.

    Neutropenia: Neutropenia is another hematological side effect that can occur as a result of Car-T therapy. Neutrophils are a type of white blood cell responsible for fighting infections. Due to a temporary reduction in the number of neutrophils, leading to neutropenia patients may be more susceptible to infections and can prolong the healing process. Common symptoms of neutropenia include fever, chills, sore throat and skin infections.

    car t side effects

    Car-T therapy at Sheba: Sam Turel’s Story

    After he was diagnosed with chronic lymphocytic leukemia (CLL) in 2009, Sam Turel began receiving treatment in his native India. Following seven years in remission, he suffered a relapse and was treated with targeted therapy. Unfortunately, his cancer took a turn for the worse and transformed from CLL to diffuse large B-cell lymphoma (DLBCL). After attempts to treat it with chemotherapy failed, Sam began to research other options, and eventually turned to Sheba Medical Center for Car-T therapy. Fast forward to the present day and Sam is healthy, happy and enjoying his retirement years.
    How I took charge of my disease: Car-T therapy at Sheba Medical Center

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