The F.D.A. recently approved Aucatzyl, a CD19 CAR-T therapy for B-ALL leukemia in adults. It joins a handful of other approved CAR-T therapies designed to treat various forms of cancers, including multiple myeloma. But it’s worth looking at Aucatzyl, in particular, because it has some unique aspects…
But first: CAR-T therapy stands for chimeric antigen receptor T cell therapy. It’s a form of immunotherapy that modifies a patient's own T cells (a type of white blood cell) to detect and attack cancer cells. How it works, basically, is that researchers take T cells from a patient, engineer them to express receptors specific to cancer cell surface proteins, and then reinfuse those cells into the patient’s bloodstream. Once inside the body, the engineered T cells grab onto cancer cells and destroy them using cytotoxic mechanisms (like punching holes in the cancer cell membrane using perforins).
In the case of B-ALL, the T cell receptor that gets expressed binds CD19 — a protein commonly found on the surface of B cells, including cancerous ones. There are existing CAR-T therapies targeting this protein — including Tecartus — but Aucatzyl’s approach is distinct.
Like many other cell therapies, Aucatzyl uses a lentiviral vector to deliver a CAR-encoding gene into a patient’s T cells. But the CAR protein that it carries was designed to have a high dissociation rate. In other words, when a T cell engineered to express this “special” CAR grabs onto a cancer cell, it delivers its cytotoxic payload and then disengages from the B cell more rapidly than other immunotherapies. This rapid release allows the T cell to move on and attack multiple cancer cells in succession — a phenomenon known as "serial killing” — which enhances its tumor-killing efficiency.
In a clinical trial with 65 patients, 42% achieved complete remission within three months of receiving Aucatzyl, with a median remission duration of 14.1 months. Severe cases of cytokine release syndrome — a common and potentially dangerous side effect of CAR-T therapies — were reported in just 3% of patients, which is lower than other therapies.
Unfortunately, all cell therapies are complex and expensive to manufacture. If we want these therapies to reach more patients, we’ll need to find ways to slash costs and make them at larger scales. At Asimov, we’re building a platform, called LV Edge, that combines wet-lab and computational tools to make lentivirus manufacturing and payload design much easier — and cell therapies cheaper.
ALT Source: NCI https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy