October 25, 2021

I, Science

The science magazine of Imperial College

Monoclonal antibodies attached to cytotoxic drugs act as homing missiles that destroy cancers from their core ...

fp_smart-bomb_mainWe’ve zapped it. We’ve blocked hormones. We’ve chopped it out. We’ve hit it hard with toxic chemicals. We’ve even used specialist antibody therapies. But some cancers still won’t relent. What more is there to do? What can medical science conjure up now?

A new experimental approach to cancer therapy could employ ingenious ‘smart bombs’ to home in on cancer cells in the body and deliver a payload of cancer-killing drugs, while leaving the rest of the body intact.

These little homing missiles are a class of drug known as antibody-drug conjugates (ADCs), and are at the forefront of today’s cancer research and development. But the main constituents of an ADC aren’t that new. The recipe includes a monoclonal antibody, which is an antibody that’s very selective about what it binds to, and a cytotoxic cancer-killing drug that has been traditionally used in cancer treatment for many years. The monoclonal antibody and the cytotoxic drug are connected by a ‘linker’.

The genius of this hybrid drug is that it harnesses the cancer-binding specificity of the monoclonal antibody to guide the cytotoxic drug right into the heart of the cancer, leaving the healthy cells in the rest of the body well alone. The ADC travels in the blood stream and, when the arms of the antibody come into contact with a cancer cell, the cytotoxic ‘warhead’ penetrates and destroys the cell from the inside out.

So far, two ADCs have been designated as fit for use by drug regulators: Adcetris for the treatment of several types of lymphoma; and Kadcyla for a form of breast cancer. ADCs are certainly attracting a lot of attention in the pharmaceutical industry, and research is underway to develop further ADCs against a variety of other cancers. Challenges in ADC development include improving the linker technology so that the cytotoxic drug does not break away from the antibody in the bloodstream. A further challenge is to fully ensure the monoclonal antibody discriminates between cancerous and healthy cells.

Overall, ADC development is enormously exciting and could well be a step towards Nobel laureate Paul Ehrlich’s century-old vision of a ‘magic bullet’ to beat cancer.