What Is CAR T-cell Therapy?
CAR T-cell therapy, or chimeric antigen receptor T-cell therapy, is an immunotherapy that uses genetically altered T cells to target and destroy cancer cells. This treatment is FDA-approved to treat several types of blood cancer, including acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
CAR T-cell infusion combines three types of therapy:
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Cell therapy;
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Immunotherapy;
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Gene therapy.
The leukapheresis process, where white blood cells are harvested, is a critical step in therapy preparation.
The studies show 60% of patients with B-cell lymphoma go into remission for at least 5 years. That’s why CAR T cell therapy is a “living drug” that has a long-term effect on destroying cancer cells.
Source - National Cancer Institute
How Do CAR T Cell Therapies Work?
The process begins with the collection of the patient’s T cells, a type of white blood cell that plays a crucial role in the immune response. Once the T cells are modified, they are expanded in number and reinfused into the patient’s bloodstream.
The CAR allows these engineered T cells to identify and attach to cancer cells, marking them for destruction. This targeted approach ensures that the immune system can effectively attack cancer cells while minimizing damage to healthy cells.
CAR T cell therapies work by:
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Identifying and targeting specific cancer cells;
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Activating the immune system to attack cancer cells;
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Enhancing the body’s natural ability to fight cancer;
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Providing a personalized treatment approach.
Who Is a Candidate for CAR T-cell Therapy?
CAR T-cell therapy is not a one-size-fits-all treatment. It's typically considered for patients with specific types of cancer, including:
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Relapsed or refractory Acute Lymphoblastic Leukemia (ALL). The patients whose leukemia has returned after initial treatment or hasn't responded to existing therapies.
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Relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL). The patients with a specific type of aggressive lymphoma that has recurred or failed to respond to other treatments.
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Multiple Myeloma. CAR T-cell therapy for multiple myeloma shows great results in destroying damaged bone marrow cells.
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Follicular Lymphoma. The patients with affected lymph nodes develop small, round nodules called follicles.
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Refractory mantle cell lymphoma. The patients with a subtype of B-cell non-Hodgkin lymphoma who suffer from lymph node enlargement and don't respond to traditional chemotherapy.
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Other types of blood cancers. Research is ongoing to explore CAR T-cell therapy's effectiveness in treating other blood cancers and potentially some solid tumors.
What Factors Have an Impact on Patient's Potential?
Here's the list of standpoints that make a patient more or less suitable for undergoing CAR T-cell treatment:
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Age and overall health. Younger patients with a more robust immune system are better candidates.
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Specific cancer type. T-cell therapy is most effective for certain cancer types (leukemia and lymphoma).
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Prior treatments. Patients who haven't responded well to other treatments may be suitable candidates.
What Are the Safety Concerns Associated with CAR T-cell Treatment?
While CAR T-cell therapy offers promising results, there are potential safety concerns, including:
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Cytokine Release Syndrome (CRS) is a common side effect (42-100% of patients), which includes fever, chills, fatigue, and difficulty breathing. It usually occurs within a few days of receiving the CAR T-cells and can be managed with medication (antipyretics or corticosteroids for advanced cases).
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Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) is a less common (3-64% occurrence rate) but more serious side effect affecting the nervous system. It may cause confusion, tremors, headaches, and difficulty speaking.
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Tumor lysis syndrome (TLS) occurs when large numbers of cancer cells are rapidly destroyed, leading to electrolyte imbalances and kidney problems.
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Risk of infection. Due to the suppression of the immune system during treatment, patients are more susceptible to infections.
What Are the Differences Between CAR-T Cell Therapies and Other Immunotherapy Treatments?
There are several key differences between CAR T-cell therapy and other immunotherapy approaches (such as targeted therapy and monoclonal antibodies):
| Feature | CAR T-cell Therapy | Other Immunotherapies |
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Mechanism of Action |
Genetically modified T-cells target specific antigens on cancer cells. |
Stimulates the body's immune system to recognize and attack cancer broadly. |
|
Specificity |
Highly targeted towards particular cancer cells. |
It can have a broader effect on the immune system. |
|
Customization |
Personalized treatment using the patient's T-cells. |
Not personalized. |
|
Administration |
Requires complex procedures for T-cell extraction, modification, and reinfusion. |
It can be administered through injections or infusions. |
The other table shows precise differences between CAR T-cell therapy and the most common cancer treatments.
|
Feature |
CAR T-cell Therapy |
Chemotherapy |
Stem Cell Transplant |
|
Target cells |
ONLY tumor cells. |
ALL the cells that are rapidly dividing (including healthy tissues). |
Not defined. |
|
Type of cells |
Patient’s OWN immune cells. |
Not defined. |
Donor’s cells. |
What Are the CAR T-Cell Therapy Side Effects?
CAR T therapy is a one-time treatment. Once the CAR T cells are back in the body, they can fight cancer immediately.
Despite the safety concerns mentioned earlier, CAR T-cell therapy can cause other side effects, including:
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Fatigue;
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Nausea and vomiting;
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Low blood counts;
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Fever;
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Hair loss;
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Mouth sores.
These side effects are usually temporary and manageable.
What to Expect Before, During, and After Treatment?
Before receiving CAR T-cell therapy, patients may undergo a conditioning regimen of lymphodepleting chemotherapy (which reduces the number of damaged lymphocytes). This preparatory step aims to reduce the presence of existing immune cells, thereby minimizing the risk of the body rejecting the infused CAR T cells.
The administration of CAR T cells involves a relatively straightforward procedure. The engineered cells are infused intravenously, similar to receiving blood, and the process typically takes between 5 and 30 minutes.
Following CAR T-cell therapy, patients often require hospitalization for 7 to 10 days to allow for close monitoring and management.
Do Patients Still Need Stem Cell Transplants After CAR T-Cell Therapy?
Allogenic stem cell transplant (allo-HCT) is a standard treatment for B-cell lymphomas, but it often doesn't work for long. Patients may have relapses even after the transplant. As a type of immune cell therapy, CAR T-cell treatment for cancer can be combined with allo-HCT to speed up the remission.
The studies show that patients with CAR T-cell therapy alone lived for an average of 10.5 months. On the contrary, those who had transplantation after the T-cell treatment had an average survival of 70.2 months. This is an excellent example of how combining cancer treatments improves patient outcomes.
Stem cell transplantation is also an option for the following cases:
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When lymphoma/multiple myeloma doesn't respond to CAR T-cell therapy;
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When the initial disease relapses multiple times;
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After the previous stem cell transplantation.
What Are the Top Hospitals Offering CAR T-Cell Therapy?
Bookimed has selected the top CAR T-cell centers using our Smart Ranking System. This system considers various factors, such as:
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Doctor's experience;
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Success rates;
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Technological advancements;
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Patient satisfaction.
By leveraging this data-driven approach, we ensure our patients can access the most effective and cutting-edge treatments available. The choice is always yours, and we highly recommend consulting with our medical coordinators before signing up for the treatment.
Here's the list of the best hospitals where is car t-cell therapy available:
Sourasky Medical Center (Ichilov), Israel
The Hematology Institute is a leading CAR T-cell therapy clinic in Israel. Their experts have much experience treating patients with CAR T-cells and managing any side effects. The center has a 90% success rate in oncology clinical trials and treatments.
Dr. Ron Ram is one of the best hematology/oncology department specialists. He has performed numerous stem cell transplants and contributed to chimeric cancer treatment.
The Ichilov was also the first CAR T hospital in Israel to get government approval.
Beijing GoBroad Boren Hospital, China
The head of the oncology department, Dr. Guo Li Gai, has studied thousands of CAR T-cell therapy for non-Hodgkin lymphoma cases to administer effective CAR T-cell therapy for his patients.
The hospital's oncology department works closely with the Mayo Clinic. The doctors use a system called MICM to make accurate cancer diagnoses. Here's what they evaluate:
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Shape of cells (morphology);
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Specific substances (immunology);
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Chromosomes (cytogenetics);
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DNA of cells (molecular science).
Besides collecting stem cells, the local laboratory also separates and cryopreserves their components for later use. This can benefit urgent cases for patients in the last stages of cancer.
SJD Barcelona Children’s Hospital, Spain
Sant Joan de Déu is known for its technological advances and discoveries. The specialists here were the first in Spain to develop a vaccine against tumors of the brain and medulla, as well as a nanofiber tissue for local cancer treatment.
The cell therapy center accepts children and young adults up to 21 years old. It has the best conditions for both bone marrow transplantation and CAR T-cell therapy. The cancer center has 4 boxes with HEPA filters and positive pressure for transplant-eligible patients.
Is CAR T-Cell Therapy Suitable for Solid Tumors?
While CAR T-cell therapies have shown significant success in treating blood cancers, their application in solid tumors (such as sarcomas, carcinomas, and lymphomas) presents unique challenges.
Solid tumors have a complex microenvironment that can hinder CAR T cells from effectively reaching and attacking the tumor site. This has made it difficult to achieve the same level of success seen in blood cancers.
However, researchers are actively exploring new strategies to overcome these obstacles, including:
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Developing CAR T cells that can target specific proteins on solid tumor cells;
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Using CAR T-cell therapies in combination with other treatment methods to enhance their effectiveness;
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Investigating the use of CAR T cells in combination with other treatments, such as checkpoint inhibitors or chemotherapy.
CAR T-cell therapy has the potential to help many patients with solid tumors. More research is needed to learn how it works and find new ways to use it.
How Can Bookimed Help You Find the Best Hospital for CAR T-Cell Therapy?
Finding the right center for CAR T-cell therapy can be challenging. Bookimed coordinators will be happy to assist you with:
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Applying to reputable hospitals. Our medical partners have well-trained staff and expertise in CAR T-cell therapy programs.
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Transparent cost estimates. We will calculate all the potential costs associated with treatment abroad.
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Travel arrangements. We will arrange flights, accommodation, and local transportation.
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Language assistance. Our coordinators will provide translation services to ease your treatment journey.
References
CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?. PubMed Central (PMC). URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470158/ (date of access: 23.09.2024).
CAR T-cell Therapy and Its Side Effects. Information and Resources about Cancer: Breast, Colon, Lung, Prostate, Skin | American Cancer Society. URL: https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell1.html (date of access: 23.09.2024).
CART Cell Therapy Toxicity - StatPearls - NCBI Bookshelf. National Center for Biotechnology Information. URL: https://www.ncbi.nlm.nih.gov/books/NBK592426/ (date of access: 23.09.2024).
Long-term outcomes following CAR T cell therapy: what we know so far - Nature Reviews Clinical Oncology. Nature. URL: https://www.nature.com/articles/s41571-023-00754-1 (date of access: 23.09.2024).