An Overview of 8 Drugs for Acute Lymphoblastic Leukemia (ALL) Treatment
Posted: Apr 01, 2021
Acute lymphoblastic leukemia (ALL) is a kind of cancer affecting white blood cells, whose function is to fight infection and thus protect human body against various diseases. Patients suffering ALL develop a large number of immature white blood cells in their bone marrow, leading to malfunction of fighting infections.
ALL mainly affects a type of white blood cell, lymphocytes, causing them to build up in the liver, spleen and lymph nodes. ALL can be divided into two main subtypes: T-cell lymphoblastic lymphoma/leukemia, which occurs more often in adults than in children, develops from T lymphoblasts; B-cell lymphoblastic lymphoma/leukemia, the most common ALL subtype, develops from B lymphoblasts. At present, the main treatment drugs for ALL are as follows:
Philadelphia Chromosome Positive (Ph + ALL) Tyrosine Kinase Inhibitor (TKI)
In the body of approximately one-quarter of ALL patients, leukemia cells have Philadelphia chromosomes. This is an abnormal chromosome formed by the exchange of genetic material between chromosomes 9 and 22, which produces a gene mutation called BCR-ABL. Cells with the BCR-ABL gene produce abnormal proteins that help cell growth. Tyrosine kinase inhibitor (TKI) drugs that attack this abnormal protein include:
Imatinib is the first generation of Ph(+) TKI, and can be used for chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), gastrointestinal stromal tumor (GIST), systemic mastocytosis (SM), myelodysplastic syndrome (MDS), etc.
Dasatinib is a TKI that targets Philadelphia chromosome and Src gene mutations. It is mainly used for the treatment of imatinib resistance. The drug has also been proven to treat many other types of cancer, including prostate cancer.
Nilotinib is a selective Bcr-Abl kinase inhibitor, which is 10-30 times more effective than Imatinib in inhibiting Bcr-Abl tyrosine kinase activity and the proliferation of Bcr-Abl expressing cells.
Ponatinib is currently the only BCR-ABL TKI against T315I mutation, which can effectively block the T315I mutation of ABL1 gene. This mutation is one of the common resistance mechanisms of the first two generations of BCR-ABL TKI.
Bosutinib is a dual kinase inhibitor of both the BCR-ABL and Src tyrosine kinases, which is for the treatment of patients with chronic myelogenous leukemia (CML) resistant to or intolerant of other BCR-ABL1 inhibitors and may also be beneficial for Ph(+) ALL.
Immunotherapy Drugs for ALL
Antibodies are proteins produced by the human immune system that help fight infection. Man-made versions of these proteins are called monoclonal antibodies, which can be designed to attack specific targets, such as proteins on the surface of leukemia cells.
6. Blincyto (Blinatumomab)
Hematology is within the range of bispecific antibody application. Blincyto (Belintumumab) is a kind of bispecific antibody targeting CD19 and CD3. It was approved at the end of 2014 by the United States Food and Drug Administration (FDA) for the treatment of Ph(-) relapsed/refractory B-cell precursor acute lymphoblastic leukemia.
Blinatumomab is a special monoclonal antibody because it attaches to two different proteins at the same time. CD19 protein is present on B cells, including some leukemia and lymphoma cells, and CD3 is a protein on T cells. This medicine is usually used after chemotherapy.
7. Besponsa (Inotuzumab ozogamicin)
Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) of CD22 antibody (Inotuzumab) and Ozogamicin. This medicine is usually used after chemotherapy.
8. Kymriah (Tisagenlecleucel) CAR-T cell therapy
Kymriah is the first CAR-T cell immunotherapy approved by the FDA to target the CD19 protein on certain leukemia cells. It can be used for children and young people under the age of 25 to treat B-cell ALL that relapses after treatment or no longer responds to other treatment. This type of treatment is only performed in medical centers that have received special training.
"Targeted therapy, combination therapy and cell therapy developed in recent years have pushed the treatment of ALL to another climax. Currently, many immunotherapies, including ADCs, CAR-T cells and bispecific antibodies, are currently undergoing clinical evaluation or are in the pre-clinical development stage. It is believed that the advancement of biotechnology can further increase the cure rate of ALL." said a scientist at Creative Biolabs, a biotechnology company focusing on bispecific antibody development services.
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