Dr. Rafael Amado, President, Head of Global Research and Development at Zai Lab, highlights the renewed interest in antibody-drug conjugates (ADCs) with advancements in linker technology and payload delivery, leading to improved therapeutic windows and reduced side effects. The Zai Lab lead ADC ZL-1310 has shown promising results in small cell lung cancer and the ability to cross the blood-brain barrier to treat brain metastases, a common complication in small cell lung cancer. Combining ADCs with immunotherapy can potentially enhance the immune response.

Rafael elaborates, "ADCs have undergone a bit of a renaissance. In the past, traditional ADCs had many drawbacks. They had what's called a narrow therapeutic window. So the dose that was effective was very close to the dose that was toxic. This was due to many factors. The construction of the antibodies and the chemotherapy, which we call payload, wasn't liberated in the right compartment. Either the tumor microenvironment or the antibody was not well internalized and didn't go into the cancer cell."

"There are now new generations of antibody-drug conjugates, and ZL-1310 is one of them. It uses a technology called TMALIN. The advantage of this is that the linker is quite specific and the antibody internalizes, it can release the payload, which is a different chemotherapy, than a classic ADC. Also, it can be digested in the tumor microenvironment, and the chemotherapy can penetrate cells that don't have the target just by influx into the cell. So that's called the bystander effect."

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