Exploiting Synthetic Lethality in Cancer Immunotherapy through Engineered Dual-Specificity T Cells

Jeya Chelliah B.Vsc Ph.D.

Imagine you’re driving a car that has two separate brake systems (let’s call them A and B). Under normal circumstances, you use either A or B to stop your car, and having both systems ensures that if one fails, you can still rely on the other to stop safely.

This redundancy is similar to how some processes work inside our cells; there are backup systems in place to keep the cell alive if one system fails.

Now, let’s apply this to cancer and the concept of synthetic lethality. In our analogy, suppose system A is damaged in a cancer cell, but the cell doesn’t die because it still has system B to rely on. In a healthy, non-cancerous cell, both A and B are working fine.

Synthetic lethality in cancer treatment is like finding a way to specifically target and disable system B in cells where system A is already damaged (the cancer cells). When both systems A and B are disabled, the cancer cell can no longer survive and dies. However, in healthy cells where both systems are intact, disabling just one (either A or B) won’t be lethal because the other system can compensate, allowing these cells to live.

So, the essence of synthetic lethality is to find and exploit these unique pairs of vulnerabilities in cancer cells—targeting the backup system only in cells that have a specific primary system failure—while leaving healthy cells unharmed. It’s like creating a smart bomb that only stops cars with a specific broken brake system, leaving all other cars on the road safe and operational.