CAR-T therapy

Written by RegMedNet

What is CAR-T?

Chimeric antigen receptor-T cell (CAR-T) therapy takes a patient’s own T-cells, which coordinate the immune system and respond lethally to invading pathogens, and engineering them to have special receptors on their surface. These artificially-added receptors mean they can recognize and attack cells and foreign bodies which might previously have been hidden from them, such as tumors. Each CAR is engineered specifically to the antigen on that foreign body it needs to find and attack. CAR-T cells are completely synthetic molecules; they don’t exist in nature.

How does CAR-T work?

Firstly, a sample of patient blood is collected and the T-cells separated out. Next, using a delivery vector, most commonly a deactivated virus, the engineered CARs are attached to the T-cell surface. Hundreds of millions of CAR-T cells are needed for the final dose, so next the CAR-T sample is expanded. Finally, the CAR-T cells are infused back into the patient, where they can seek out and target the antigens the CARs were programmed to hunt for.

History of CAR-T

Immune cells were demonstrated to have the ability to target and kill cancer cells as early as 1960 but immunotherapy wasn’t successfully administered until 1973, when bone marrow transplants were used to regenerate blood cell supplies following chemotherapy. Just a few years later, in 1986, tumor-infiltrating lymphocytes were used to treat patients at the National Cancer Center. MIT (MA, USA) proved to be the site of the first attempts at T-cell engineering, starting in 1992, and just a year later, the first CARs were developed; however, these did not persist long enough in the body after administration for an effect to be seen.

The first effective CAR-T cells were not seen until 1998. Various milestones were checked off throughout the 90s and early 00s, and in 2013, the regenerative medicine industry was able to read the results of the first ever human clinical trial utilizing CAR-T therapy. Here, CD19 CAR-T cells were used to treat adults with acute lymphoblastic leukemia (ALL), an aggressive form of cancer which had very few treatment options and was the leading cause of death in childhood cancer patients.

In 2017, CRISPR was used to further optimize CAR-T cells, improving their effectiveness and later that year, the FDA gave the first CAR-T therapy its approval. Nowadays, further progress is being made to improve the effectiveness and safety of the latest generation of CAR-T therapies, and applying them to more and more types of cancer.

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