Pembrolizumab, known commercially as Keytruda, represents a significant advancement in cancer treatment. This immunotherapy drug works by harnessing the body’s own defense mechanisms to fight malignant cells. Understanding how it operates involves delving into the intricate relationship between cancer and the immune system.
How Cancer Hides from the Immune System
The human immune system possesses a sophisticated ability to detect and eliminate abnormal cells. Specialized immune cells, particularly T-lymphocytes or T-cells, are equipped to recognize specific markers on the surface of unhealthy cells. When these T-cells identify a cancerous cell, they are programmed to initiate an attack, aiming to destroy the threat.
Cancer cells, however, are highly adaptive and can evolve various strategies to evade this immune surveillance. One common tactic involves altering their surface characteristics, making it difficult for T-cells to distinguish them from healthy cells. This allows them to blend in and escape detection by the patrolling immune forces.
Beyond camouflage, cancer cells can also actively suppress the immune response. They achieve this by emitting signals that tell the immune system to stand down. These inhibitory signals act like “brakes” on the immune system, preventing T-cells from fully activating and carrying out their destructive function against the tumor. This evasion is a major hurdle in the body’s defense against cancer.
Immune Checkpoints: The Body’s Balancing Act
The body maintains a balance within its immune system, ensuring it can fight off threats without mistakenly attacking healthy tissues. This balance is regulated by “immune checkpoints,” which are molecules on immune cells that act as switches. One such checkpoint pathway involves the protein Programmed Death-1 (PD-1), which is found on the surface of T-cells.
PD-1 interacts with the protein Programmed Death-Ligand 1 (PD-L1), which can be found on the surface of some healthy cells. When PD-1 on a T-cell binds to PD-L1 on another cell, it delivers an inhibitory signal, effectively deactivating the T-cell. This interaction helps prevent autoimmune reactions, where the immune system attacks the body’s own healthy cells.
Cancer cells have learned to exploit this regulatory mechanism. Many cancer cells express high levels of PD-L1 on their surface. By presenting abundant PD-L1, these cancer cells can bind to the PD-1 receptors on nearby T-cells. This interaction sends a “do not attack” signal, disarming the T-cells that would otherwise destroy the tumor.
Pembrolizumab’s Mechanism of Action
Pembrolizumab is a monoclonal antibody, a protein engineered to target a molecule. It is designed to bind with high specificity to the PD-1 receptor on the surface of T-cells. This binding is a precise interaction, much like a key fitting into a lock.
When pembrolizumab attaches to the PD-1 receptor, it blocks the site where PD-L1 would bind. This action prevents the inhibitory interaction between PD-1 on the T-cell and PD-L1 on the cancer cell. Pembrolizumab acts as a shield, preventing the cancer cell’s “off” signal from reaching the T-cell.
By blocking the PD-1/PD-L1 interaction, pembrolizumab releases the brakes on T-cells. With this inhibitory signal disrupted, the T-cells are no longer suppressed and can regain their full activation potential. This allows them to recognize the cancerous cells, initiating an immune response. Reactivated T-cells then proliferate, migrate to the tumor site, and destroy the malignant cells, unmasking the cancer to the immune system.