The complete guide to CAR T-cell therapy

  • What is CAR T-cell therapy?

    CAR T refers to chimeric antigen receptor T cell. CAR T-cell therapy is a type of immunotherapy that uses specially altered T cells —derived from our immune system — to fight cancers. Usually during the process, a sample of a patient's T cells are collected from the blood, then processed to produce special structures (which is chimeric antigen receptors (CARs) on their surface). When these CAR T cells are reinfused into the patient, the new receptors enable them to latch onto a specific antigen on the patient's tumor cells and kill them.

     

    Figure 1. Engineering CAR T cells

     

    CAR T-cell therapy has become a hot research area in recent years and scientists believe it has many promising applications. Here in this article, we will summarize 10 facts that you may want to know about it.

    1. What are some advantages of CAR T-cell therapy?

    (1). It’s simple to be administrated for patient since CAR T-cell therapy is a single infusion that usually requires at the most two weeks of inpatient care, and then it’s done. Compared to newly diagnosed non-Hodgkin’s lymphoma or childhood leukemia patients which usually need at least half year or more of chemotherapy, it is quite simple.

    (2). It is a living drug, and its benefits can last for many years. Once those cells enter human body, they can “live” in a long-term, and they will still recognize and attack cancer cells if and when there’s a relapse. An example is CD19 CAR T-cell therapy.

    1. How can a patient know when he could use a CAR T-cell therapy?

    It’s not complicated for a patient to look for a CAR T-cell therapy if the patient has already been through two lines of unsuccessful treatment, he/her can get the Food and Drug Administration (FDA)-approved commercial product. Or else the patient needs to go through a clinical trial if he/her wants it as first line or second line therapy, or want to use it for a different type of lymphoma

    1. What types of patients can receive CAR T-cell therapy?

    Currently it is only approved to treat a small number of patients: leukemia and non-Hodgkin lymphoma. And both approvals significantly limit the type of patients who can undergo the treatment.

    1. Does it work better on blood cancers?

    CAR T-cell therapy has only been approved for blood cancers to date, which means it indeed works better on blood cancers. However, clinical trials measuring its performance on solid tumors have not been encouraging.  

    1. What side effects CAR T-cell therapy may cause?

    Unlike chemotherapy side effects (such as hair loss, nausea, and vomiting), there are still some risks of significant side effects with CAR T-cell therapy. Possible side effects from CAR T-cell therapy include:

    • Cytokine release syndrome: CAR T cells can initiate a massive release of substances called cytokines, which triggers an inflammatory condition known as cytokine-release syndrome (CRS). Symptoms may be flu-like, with a high fever and/or chills; low blood pressure; difficulty breathing; or confusion. These symptoms can be mild or severe.
    • Neurologic difficulties: Patients may also experience confusion, difficulty understanding language and speaking, or stupor.
    1. How long it takes for the full treatment to be completed?

    There are many steps for the treatment to be processed. They are Evaluation (a few tests and screenings are operated on patients to determine if CAR T-cell therapy is an appropriate option), Collection (T cells are collected from patients via apheresis), Engineering (The T cells are genetically engineered to express chimeric antigen receptors on their surface), Multiplication (The genetically modified T cells are "expanded" in laboratory), Conditioning Therapy (Prior to infusion of the CAR T cells, patients may receive chemotherapy for their cancer. This helps to create space in your immune system for the infused CAR T cells to expand and proliferate), InfusionRecovery. The whole process will take months to be fully finished.

    1. Does the cell therapy will be long-term effective?

    We know that T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity. They attack harmful cells or viruses, and are programmed to remember harmful substance if they attack again. CAR T-cells are the same. As long as the process works normally, they are designed to be on guard duty for the rest of the patient's life.

    1. Do you know some FDA-approved CAR T-cell Therapies?

    Yes. In 2017, Tisagenlecleucel was the first CAR T-cell therapy to receive FDA approval. FDA approved axicabtagene ciloleucel (Yescarta) for the treatment of diffuse large B-cell lymphoma (DLBCL). And then on May 1, 2018, FDA approved another CAR T-cell therapy, tisagenlecleucel (Kymriah), for adults with certain types of non-Hodgkin lymphoma.