Chimeric Antigen Receptor (CAR) T-cell therapy represents a significant advancement in cancer treatment. This approach harnesses the body’s immune system to combat cancer. CAR T-cell therapy modifies a patient’s immune cells, enabling them to specifically recognize and eliminate cancer cells. This therapy has shown success, particularly in treating certain blood cancers.
What Are CAR T Cells?
T cells are white blood cells that play a role in the body’s immune system, identifying and fighting infections and abnormal cells. For CAR T-cell therapy, these T cells are collected from a patient’s blood through apheresis.
Once collected, T cells are sent to a laboratory for genetic modification. A new gene, encoding a Chimeric Antigen Receptor (CAR), is introduced into them. This engineered CAR is a synthetic receptor designed to target a specific antigen. The modified T cells are then expanded in the lab, creating millions of specialized CAR T cells, before being infused back into the patient.
How CAR T Cells Find Their Targets
Upon infusion back into the patient, these genetically modified CAR T cells begin their search. They circulate throughout the body, seeking specific markers, antigens, present on the surface of cancer cells. This targeted recognition allows CAR T cells to distinguish cancerous cells from healthy ones.
CAR T cells navigate the body until they encounter cells displaying their target antigen. Once a CAR T cell recognizes its target antigen, it binds to the cancer cell, initiating a cascade of events to eliminate the threat.
The Science of Specific Binding
The CAR on the T cell interacts with the antigen on the cancer cell through a precise “lock and key” mechanism. The CAR is a complex protein composed of several components. It includes an extracellular antigen-binding domain, a single-chain variable fragment (scFv), which acts as the “key” designed to fit a “lock” on the cancer cell’s surface.
This scFv is connected to a transmembrane domain, which anchors the CAR to the T cell membrane, via a hinge or spacer region. The hinge provides flexibility, allowing the antigen-binding domain to better access and bind to the target antigen. Upon successful binding of the scFv to the tumor antigen, signals are transmitted through the intracellular signaling domains of the CAR, which activate the T cell. This precise fit is important for the CAR T cell to recognize and engage with the cancer cell effectively.
Why Precise Binding Matters
Precise binding is important for the effectiveness and safety of CAR T-cell therapy. This specificity ensures that CAR T cells target and attack cancer cells, minimizing harm to healthy tissues.
Activation leads to the CAR T cell multiplying and releasing cytotoxic substances like perforin and granzymes, which directly destroy the cancer cell. Activated CAR T cells also release cytokines that recruit other immune cells to the tumor site, amplifying the anti-cancer response. Conversely, if binding is not sufficiently precise, it can lead to “on-target, off-tumor” effects, where healthy cells expressing the target antigen are inadvertently attacked, causing severe side effects, such as cytokine release syndrome.