In this article, we will discuss about CAR T-Cell Therapy: Definition, Works, Cost, 7 Side Effects, and Clinical Evidence.
July 12, 2017 is a historic day for the development of gene and cell-based therapies in the world. On that day the FDA approved CTL019 (tisagenlecleucel) of Novartis as a therapeutic option to cope with relapsed or refractory B-cell acute lymphoblastic leukemia in children and adolescents.
What is CAR T cell therapy?
In principle, CTL019 is a modified T Cell, chimeric antigen receptor (CAR) derived from the patient’s own body and inserted in the Lentivirus vector. CAR is specific to Antigen B cell CD19, which can be identified by CTL019 and then eliminated. CD3-ζ and 4-1BB are part of CAR which is responsible for antitumor activity.
A look at how CAR-T cell therapy works
Chemotherapy, radiotherapy, immunotherapy, and surgery are some common treatments to cure cancer. The CAR-T is part of immunotherapy.
The work of CAR-T is slightly different from the usual treatment. T cells (one of the immune components of the body) the patient is taken, and the cell is modified some time in the laboratory to be able to recognize and attack the cancer cells. Afterwards, the T cell is re-injected into the body. This process is called adoptive cell transfer (ACT).
From there, this cell is expected to stop the progression, kill, and prevent the spread of cancer cells in the body.
CAR-T therapy cost
The CAR-T therapy cost for one treatment is quite expensive to reach US $450,000 per treatment. The price was far above the method of treatment through stem cell transplantation, which cost about US $60,000 – US $120,000 depending on where the stem cell was obtained.
CAR T-Cell Therapy Side Effects
Patients should be strictly observed in the hospital during obtaining this therapy due to the severe side effects, such as:
- Anemia, thrombocytopenia, or Leukopenia
- Risk of infection due to bone marrow suppression and in particular due to cell aplasia B
- Blood transfusions due to risk of bone marrow suppression
- Cytokine release syndrome (CRS): fever, weakness, rash, changes in blood pressure
- Neurological complications: seizures, headache, delirium
- Long-term complications such as autoimmune diseases, heart disorders, renal failure, and liver failure may also occur.
Clinical Evidence for the Use of CAR-T therapy
T CAR Cell Therapy has successfully detected and destroyed cancer cells that have CD19 antigen. CD19 is an antigen on the surface of the B lymphocytes, CD19 is significantly expressed and some types of blood cancers, such as chronic lymphocytic leukemia and acute lymphoblasttic leukemia.
Clinical trial studies show that immunotherapy with T CAR cells targeting CD19 (CAR T cell CD19) provides clinical success in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia.
Clinical trials in 51 acute lymphoblastic leukemia patients showed that CAR T infusion provides complete morphological remission at 41 (82%) Patients. Approximately 69% of patients undergoing complete morphological remission achieve minimal residual disease.
Another clinical trial showed that 45.5% of which achieved minimal residual disease had a free time of leukemia for 18 months.
Neurotoxicity and CRS are pretty much reported. Similar results were also found in clinical trials with non-Hodgkin lymphoma patients and chronic lymphocytic leukemia.
CAR T Cell CD19 has been produced globally. There are 4 generations of CAR T cells that have been developed to date. Biological markers / biomarkers that have been taught in addition to CD19 are Integrin Alpha V Beta 6, CAIX, CD20, CD22, CD30, CD33, CD138, HER2, FAP, CEA, and others.
Nevertheless, these antigen targets have not shown the best results as well as CD19.
Some other clinical test studies also examined the usefulness of CAR T cells in multiple myeloma and acute myeloid leukemia.
CAR T-Cell Therapy is also adapted for solid tumors, about 30 types of solid tumor antigen have been studied, such as EGF on Glioblastoma, GD2 on neuroblastoma, Mesotelin and CD3 Zeta in pleural malignant mesothelioma.
Studies on animals show promising results, but there hasn’t been a promising clinical success in the human solid tumor.
The best results are found in CAR T cells that target GD2 on neuroblastoma (remission in 3 of 11 patients) and HER2-in-a-stable disease (4 out of 17 patients).
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