CAR-T Cell therapy

CAR-T therapy is a novel form of cancer treatment using the immune system to eradicate cancer cells. Where other therapies have failed, it has occasionally been able to heal patients. This blog will highlight all that you need to know about this procedure. Read on to
find out more!

You may like to read: CAR T-Cell therapy in India

Introduction

The immune system protects the body from infection and cancer. It is made up of billions of cells that are classified into many categories.

Lymphocytes are a type of white blood cell that make up a significant part of the immune system. Lymphocytes are divided into three categories.

• B lymphocytes (B cells) make antibodies to fight infection.
• T lymphocytes (T cells) have several functions, including helping B lymphocytes to make antibodies to fight infection, and directly killing infected cells in the body.
• Natural killer cells also attack infected cells and eliminate viruses. 

Immunotherapy

• Is a type of treatment that utilizes the body’s own immune system to fight cancer
• Improves the body’s ability to detect and kill cancer cells
• Is based on the concept that immune cells or antibodies can recognize and kill cancer cells.

You may like to read: CAR T-Cell therapy in China

Immune cells or antibodies can be made in the lab under strict circumstances and then given to cancer patients as a treatment. Several forms of immunotherapy have been licensed for use or are being studied in clinical studies to see how successful they are in treating specific cancers.

Definition

A type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer. Also called chimeric antigen receptor T-cell therapy. (Source: https://www.cancer.gov/)

What is CAR T-Cell therapy?

CAR T-cell therapy, or chimeric antigen receptor treatment, is a new type of immunotherapy that uses specially engineered T cells to more precisely target cancer cells. The immune system is made up of cells and organs that work together to keep the body safe from infection and cancer. T cells are one type of cell that hunts down and kills aberrant cells, including cancer cells. Because cancer cells can sometimes elude the immune system, it is necessary to retrain the immune system to recognise and fight cancer cells. CAR T-cell therapy is a novel way of training the immune system to fight cancer.

After a sample of a patient’s T cells is taken from the blood, the cells are re-engineered to have specific structures on their surface called chimeric antigen receptors (CARs). The receptors on these CAR T cells may aid the T cells in identifying and attacking cancer cells throughout the body when they are reinjected into the patient.

You may like to read: CAR T-Cell therapy in Malaysia

CAR T-cell therapy is now licensed by the FDA as the standard of care for certain types of relapsed or refractory non-Hodgkin lymphoma, multiple myeloma, and pediatric relapsed acute lymphoblastic leukaemia (ALL), and is being tested in additional types of blood cancer.

CAR T-Cell therapy is a form of immunotherapy that uses specially modified T-cells which are part of our immune system to fight cancer. A sample of patients T cells are collected from the blood, then it is modified to produce special structures called chimeric antigen receptors (CAR) on their surface. When these modified CAR cells are re infused in the patient, these new cells attack the specific antigen and kills the tumor cells.

How does CAR T-Cell therapy work?

CAR T-cell therapy takes help from body’s own immune system to attack and kill cancer cells. This is done by removing some specified cells from the blood of the patient, modifying them in the lab and re-injecting them into the patient. CAR T-cell therapy has produced very encouraging results in Non-Hodgkin lymphoma and thus approved by FDA.

You may like to read: CAR T-Cell therapy in Korea

Who are the right candidates for CAR T-Cell therapy ?

At present FDA has approved CAR T-Cell therapy for some forms of aggressive and refractory Non-Hodgkin lymphoma and relapsed and refractory acute lymphoblastic leukemia. Patient need to send full medical reports to ascertain the use of CAR T-Cell therapy for his treatment.

Inclusion criteria for CAR T-cell therapy :

1. Patients with CD19+ B-cell Lymphoma(At least 2 prior combination chemotherapy regimens)

2. To be aged 3 to 75 years

3. ECOG score ≤2

4. Women of childbearing potential must have a urine pregnancy test taken and proven negative prior to the treatment. All patients agree to use reliable methods of contraception during the trial period and until follow-up for the last time.

You may like to read: CAR T-Cell therapy in Singapore

Exclusion criteria for CAR T-cell therapy :

1. Intracranial hypertension or unconsciousness

2. Respiratory failure

3. Disseminated intravascular coagulation

4. Hematosepsis or Uncontrolled active infection

5. Uncontrolled diabetes.

Advantages of CAR T-Cell therapy

1. >5000 CAR T cases done by highly skilled doctor’s.
2. Hospitals in China has developed more CAR T Cell types including CD19 & CD 22 then any other country in the world.
3. China is conducting more than 300 clinical trials on CAR T Cell therapy. More than any other country on the planet.
4. Clinical effect of CAR T Cell is similar to that in USA or any other country and sometimes better.

You may like to read: CAR T-Cell therapy in Israel

Treatment process for CAR T-Cell therapy

• Complete evaluation of the patient
• T-cell collection from the body
• T-cells are then engineered in the lab
• Genetically engineered T-Cells are then multiplied by using growing them in the laboratory. These cells are frozen and then sent to the treating centres.
• Prior to infusing, patient may be given chemotherapy for their cancer. This helps the therapy work in a better way.
• Soon after chemotherapy CAR T-Cells are infused by a process which is similar to blood infusion.
• There is a 2-3 month of recovery period for the patient.

Time frame for CAR T-Cell therapy

1. Examination & test: one week

2. Pre-treatment & T-Cell Collection: one week

3. T-Cell preparation & return: two-three weeks

4. 1st Effectiveness analysis: three weeks

5. 2nd Effectiveness analysis: three weeks

Side effects of CAR T-Cell therapy

The common side effects of CAR T-cell therapy include:

• Cytokine release syndrome
  In some cases, patients may develop flu-like symptoms such as fever, chills, headache, nausea, vomiting, loose stools, and muscle or joint pains. It may also cause low blood pressure, difficulty in breathing, and a fast heart rate. These side effects are due to the release of cytokines by the immune cells during CAR T-cell therapy. These symptoms are usually mild, but can be serious and life threatening in some patients.
• Neurological events
  Neurological events can occur and can be serious in some patients. Such events include encephalopathy (brain injury and malfunction), confusion, difficulty speaking, agitation, seizures, drowsiness, altered state of consciousness and loss of balance.
• Neutropaenia and Anaemia
  Some patients may develop neutropenia or low white cell count.  Similarly, anaemia or low red blood cell count may also occur due to this therapy.
  .
  Fortunately, most of these side effects usually resolve on their own or can be managed with the use of  medications.

FDA approved therapies

• Axicabtagene ciloleucel (Yescarta^TM) is FDA approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Yescarta is also indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. It is a CD19-directed genetically modified autologous T cell immunotherapy. You can read more about this drug here.
• Brexucabtagene autoleucel (Tecartus®) is FDA approved for for the treatment of
  • Adult patients with relapsed or refractory mantle cell lymphoma (MCL).
    This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 
  • Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
    You can read more about this drug here.
• Ciltacabtagene autoleucel (Carvykti™) is FDA approved  for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. You can read more about this drug here.
• Idecabtagene vicleucel (Abecma®) is FDA approved for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. You can read more about this drug here.
• Lisocabtagene maraleucel (Breyanzi®) is FDA approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
  Limitations of Use: Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. You can read more about this drug here.
• Tisagenlecleucel (Kymriah^TM) is FDA approved for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Kymriah is also approved for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Limitation of Use: Kymriah is not indicated for treatment of patients with primary central nervous system lymphoma. It is a CD19-directed genetically modified autologous T cell immunotherapy. You can read more about this drug here.
• Tocilizumab (Actemra®) is approved for the treatment of adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS). You can read more about this drug here. 

CAR T-cell therapy continues to be available to patients who are participating in a clinical trial for indications or cancers other than the FDA approved indications. Trial protocols vary. Depending on the clinical trial, care may be provided in either a hospital setting or an intensive outpatient treatment center with experience administering cellular immunotherapy. Patients may have to stay at the treatment facility and may need to plan to stay close by before, during or following treatment. Some trial protocols require patients to confirm the availability of a caregiver before they can enroll in the trial. 

How effective is CAR T-Cell therapy ?

CAR T-cell therapy for the treatment of lymphoma and other blood cancers has shown promising outcomes. Since CAR T-cell treatment, many patients who had previously relapsed blood tumours had promising results and no evidence of cancer. It has also aided in the rehabilitation of patients who have previously failed to respond to most traditional cancer therapies.

However, longer-term studies for a larger patient population are needed to validate the efficacy of this treatment. Large-scale experiments would also aid in determining the likelihood of side effects and the right ways to deal with them.

Cost of CAR T-Cell therapy

China is a world leader of CAR-T cell therapy & BMT. Till now there are more than 300 CAR-T cell clinical trials in progress. China’s CAR-T treatment is the most budget one around the world. Because the CAR-T cell preparation is free now ! The patients only have to pay for the treatment & services. Total cost of treatment will be around $60,000 -$80,000.

You may like to read : CAR T Cell therapy in India 

How can I take CAR T-Cell therapy?

Patient can call +91 96 1588 1588 or email to cancerfax@gmail.com with patient details and medical reports and we shall arrange for second opinion, treatment plan and estimate of expenses.