Tisagenlecleucel, sold under the brand name Kymriah, is a
CAR T cells
In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific ...
medication for the treatment of
B-cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
(ALL) which uses the body's own
T cells to fight
cancer (
adoptive cell transfer).
Serious side effects occur in most patients.
The most common serious side effects are cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and decreases in platelets (components that help the blood to clot), hemoglobin (the protein found in red blood cells that carries oxygen around the body) or white blood cells including neutrophils and lymphocytes.
Serious infections occur in around three in ten diffuse large B-cell lymphoma (DLBCL) patients.
T cells from a person with cancer are removed,
genetically engineered to make a specific chimeric cell surface receptor with components from both a
T-cell receptor and an antibody specific to a protein on the cancer cell, and transferred back to the person. The T cells are engineered to target a protein called
CD19
B-lymphocyte antigen CD19, also known as CD19 molecule ( Cluster of Differentiation 19), B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene ''CD19''. In humans, ...
that is common on
B cells. A chimeric T cell receptor ("
CAR-T") is expressed on the surface of the T cell.
It was invented and initially developed at the
University of Pennsylvania;
Novartis completed development, obtained FDA approval, and markets the treatment.
In August 2017, it became the first FDA-approved treatment that included a
gene therapy step in the United States.
Medical uses
Tisagenlecleucel is
indicated
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for the treatment of those under 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse; or adults with relapsed or refractory (r/r) 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.
[ Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
In May 2022, the indication in the US was updated to include the treatment of adults with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
Adverse effects
A frequent side effect seen is
cytokine release syndrome
Cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome (SIRS) that can be triggered by a variety of factors such as infections and certain drugs. It refers to cytokine storm syndromes (CSS) and occurs when large numb ...
(CRS).
[
Serious side effects occur in most patients.]
History
The treatment was developed by a group headed by Carl H. June
Carl H. June (born 1953) is an American immunologist and oncologist. He is currently the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine of the University of Pen ...
at the University of Pennsylvania, and is licensed to Novartis.
In April 2017, tisagenlecleucel received breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory diffuse large B-cell lymphoma.
In July 2017, an FDA advisory committee unanimously recommended that the agency approve it to treat B cell acute lymphoblastic leukemia that did not respond adequately to other treatments or have relapsed.
Manufacture
In a 22-day process, the treatment is customized for each person. T cells are purified from blood drawn from the person, and those cells are then modified by a virus that inserts a gene into the cells' genome. The gene encodes a chimaeric antigen receptor (CAR) that targets leukaemia cells.
References
Further reading
BLA 125646 Tisagenlecleucel - Novartis Briefing document to FDA ODAC
External links
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