June 2021 : As per our resources, a hospital in China has developed CAR T-Cell therapy for T-cell acute lymphoblastic leukaemia (T-ALL). The expressing protein in this case is CD7. 5 patients have been tested with the therapy, and all of them achieved complete remission after the treatment. Till date, CAR T-Cell therapy has been used for the treatment of B-Cell acute lymphoblastic leukaemia (B-ALL), Lymphoma and multiple myeloma with expressing proteins such as CD19 and CD22. USFDA has approved the use of CAR T Cell therapy in B-Cell acute lymphoblastic leukaemia (B-ALL) & Lymphoma till date. CAR T-Cell therapy is the newest therapy in the treatment of deadly blood cancer and is been used in countries like the USA, UK, China, Canada, and Israel to date. Very soon, countries like India, Japan, Singapore, and South-Korea will also start using this therapy for the treatment of some types of blood cancer. Trials have already started in India on the same.
T-cell acute lymphoblastic leukaemia (T-ALL)
T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive and rapidly progressing type of acute leukaemia. It affects lymphoid-cell-producing stem cells, specifically a kind of white blood cell termed T lymphocytes, as opposed to B lymphocytes, which are usually affected by acute lymphoblastic leukaemia (ALL).
A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):
- B lymphocytes that make antibodies to help fight infection.
- T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
- Natural killer cells that attack cancer cells and viruses.
What is CAR T-Cell therapy ?
This therapy isolates immune T cells from patients, and genetically engineers these cells in vitro, loading them with “chimeric antigen receptors” (CARs) that recognize cancer cell surface antigens. Subsequently, these modified cells undergo extensive expansion in the laboratory before being infused back into the patient. There, they were like a well-trained army equipped with the latest weapons to launch a relentless attack on cancer cells.
How does CAR T-Cell therapy work?
CAR T-cell therapy takes help from the 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 China
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CAR T Cell therapy is currently available in some leading cancer institutes in USA, UK, China and Israel.
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 :
- Patients with CD19+ B-cell Lymphoma(At least 2 prior combination chemotherapy regimens)
- To be aged 3 to 75 years
- ECOG score ≤2
- 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.
Exclusion criteria for CAR T-cell therapy :
- Intracranial hypertension or unconsciousness
- Respiratory failure
- Disseminated intravascular coagulation
- Hematosepsis or Uncontrolled active infection
- Uncontrolled diabetes
Advantages of CAR T-Cell therapy
- >5000 CAR T cases done by highly skilled doctor’s.
- Hospitals in China has developed more CAR T Cell types including CD19 & CD 22 then any other country in the world.
- China is conducting more than 300 clinical trials on CAR T Cell therapy. More than any other country on the planet.
- Clinical effect of CAR T Cell is similar to that in USA or any other country and sometimes better.
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
- Examination & test: one week
- Pre-treatment & T-Cell Collection: one week
- T-Cell preparation & return: two-three weeks
- 1st Effectiveness analysis: three weeks
- 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.
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 tumour’s 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 in different countries
Approximate cost of CAR T cell therapy is different countries is given below :
USA – $ 500,000 – $ 700,000 USD
UK – $ 400,000 – $ 500,000 USD
Israel – $ 100,000 – $ 150,000 USD
Singapore – $ 400,000 – $ 500,000 USD
Korea – $ 400,000 – $ 500,000 USD
Japan – $ 500,000 – $ 700,000 USD
China – $ 40,000 – $ 80,000 USD
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
