Review Of CAR T-Cell Therapy For Cancer | M D, PharmD | RxEconsult
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CAR T-Cell Gene Therapy For Cancer Category: Cancer by - September 23, 2017 | Views: 22304 | Likes: 0 | Comment: 0  

What is CAR T-cell therapy?

Chimeric antigen receptor T-cell (CAR-T) therapy is a type of gene therapy. Gene therapy involves “editing” human DNA to target diseases at a genetic level in order to direct treatment to the source of the dysfunction. Gene therapy is changing how many diseases are prevented, treated, and cured.

CAR-T-cells are genetically engineered versions of a patient’s T-cells. T-cells are natural immune cells that have been modified with special receptors to recognize and kill cancer cells.

This type of treatment is individualized to each patient and is being investigated for the treatment of many types of cancers.

How does CAR T-cell therapy work for cancer?

T-cells are a type of white blood cell and are part of the human immune system. T-cells are taken from the patient’s blood and are sent to a special laboratory. Scientists add a gene for a special receptor that can bind proteins specific to the cancer cells by using a virus that has been made harmless. This special receptor is the chimeric antigen receptor (CAR). These CAR T-Cells are then grown and infused into the patient. Once in the patient, the modified T-cells multiply and they are able to recognize and kill cancer cells. These CAR T-Cells can replicate and persist for a long time thus providing ongoing tumor suppression and possibly long-term remission.

Advantages of CAR T-cell therapy for cancer

Lifelong Cure

As the technology progresses and research increases, there is a potential in getting the treatment to the point where it would be sufficient for one treatment to successfully cure cancer.

Treatment of many types of cancers

Theoretically, if scientists are able to identify which genes affect particular cancers they may be able to create a cure using gene therapy since genetics plays a role in human cancers.

Disadvantages of CAR T-cell therapy

Cost

Kymriah is a recently FDA approved CAR T-cell gene therapy treatment that has a price tag of $475,000 for a one-time treatment. The manufacturing process contributes to the cost of CAR T-cell therapy because every medication must be tailor-made for each patient. The cost of CAR T-cell treatment has to be weighed against its life-saving benefits. As gene therapy advances and research continues, prices are expected to go down.

Side effects of CAR T-cell therapy

Cytokine release syndrome (CRS) is one of the most common and serious adverse effects of CAR T-cell therapy. CRS is a reaction that occurs due to the release of cytokines from the T-cells. These cytokines are released into the circulation and cause symptoms such as high fever, low blood pressure, difficulty breathing, and possible hepatic, renal, and cardiac dysfunction. 79% of patients in the clinical trials for Kymriah experienced CRS. Patients with a high number of tumors, active infections, or inflammatory processes have a higher likelihood of experiencing CRS.

There is also the potential for possibly severe or life-threatening neurological toxicities may that may occur. These can occur from days to up to 8 weeks after an infusion of CAR T-cells. The symptoms include a headache, encephalopathy, dizziness, anxiety, and tremor. Disturbances in consciousness, disorientation, confusion, agitation, seizures, and aphasia may also be possible.

Kymriah (tisagenlecleucel), the first FDA approved CAR T-cell therapy

Kymriah is the first FDA approved CAR T-cell therapy. It is manufactured by Novartis and it was approved in August 2017 for the treatment of patients 25 years old or younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is resistant to other treatments or patients who have relapsed. The specific CAR in Kymriah is programmed to target the CD19 antigen which is expressed on leukemia cells.

Kymriah It has shown great therapeutic potential, producing 83% remission within 3 months in a 63 patient multicenter clinical trial.

CAR T-Cell treatments that are under development

There are currently over 300 CAR T-cell therapy clinical trials running. These trials include treatments for multiple myeloma, leukemia, lymphoma, neuroblastoma, and melanoma.

Axicabtagene ciloleucel (Yescarta), a CAR T-cell lymphoma treatment from Kite Pharma is expected to be reviewed by the FDA for approval by November 2017. It shows great potential with 36% of patients experiencing remission after 6 months of treatment.

Cellectis recently launched phase 1 trials of its CD19-targeted CAR therapy for patients with advanced acute myeloid leukemia. This treatment is off-the-shelf, meaning it is not individualized for each patient. This would help to drastically facilitate administration as well as reduce the cost of therapy.

Bluebird bio and Celgene are currently developing special CAR-T therapies that target solid tumors.

With science and technology progressing, we can expect to see even more refined CAR-T therapies that will usher in this new era of disease treatment.

Resources

CAR T-Cell therapy can lead to long-lasting remissions in patients with lymphoma

CAR T-cells: an exciting frontier in cancer therapy

Chimeric antigen receptor T-cell therapies for lymphoma

 



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