Two Antibodies Team Up To Deliver Cancer Drugs
Antigen-antibody interaction. An antigen molecule binding to a specific antibody. Antigen, complex 3D structure with multiple epitopes and antibody as a Y-shaped molecule. Immune response to infectiongettyA new...
Antigen-antibody interaction. An antigen molecule binding to a specific antibody. Antigen, complex 3D structure with multiple epitopes and antibody as a Y-shaped molecule. Immune response to infection
getty
A new antibody-based strategy uses two cancer targets to assemble a drug-delivery system, improving chemotherapy delivery to tumors that are difficult to treat with conventional antibody-drug conjugates.
Antibodies have become increasingly important in cancer treatment. Some help the immune system recognize and attack cancer cells. Others bind to specific proteins on tumor cells and carry cancer-killing drugs directly to them. These antibody-drug conjugates have transformed treatment for several cancers by concentrating chemotherapy inside tumor cells rather than exposing the entire body to the drug.
However, these therapies have a significant limitation. An antibody-drug conjugate works best when its target is present at high levels across the tumor. However, while some tumors have large amounts of the target, others have very little or none. This can leave parts of a tumor resistant to treatment.
Instead of relying on a single antibody target, a new strategy uses two antibodies that recognize different proteins on cancer cells. One helps find the tumor, and the other carries the cancer-killing drug. When the two are joined together inside the body, the combination can deliver more of the drug to tumors that would otherwise be difficult to target.
The Problem with One Target
Many antibody-drug conjugates work through the same basic mechanism: an antibody recognizes a protein on a cancer cell and carries a powerful chemotherapy drug with it. Once the antibody attaches to the cell, the cancer cell pulls the package inside, where the drug is then released.
MORE FOR YOU
This approach can be highly effective when the target is abundant. However, tumors are rarely uniform. Some cancer cells may have high levels of the target, while neighboring cells have much less.
Cancer cells can also change over time. A tumor that initially responds to treatment may reduce the amount of its target or increase another protein that helps it survive. This can make an otherwise effective antibody-drug conjugate less useful. The new approach is designed to overcome that problem by giving the drug two ways to find the cancer.
Two Antibodies, One Drug
The study focused on two proteins found on cancer cells, known as human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR). Both help control signals that regulate cell growth and are already established targets for cancer drugs. The cancer-killing drug was attached to an antibody that recognized one cell growth protein, while a second antibody recognized the other. The two antibodies were given separately, but each carried a different chemical tag designed to connect with the other.
Once both antibodies reached the body, the two tags reacted with each other and joined the antibodies together. The result was a single package that could recognize both proteins. Since not all tumors carry the same proteins at the same levels, a tumor with very little of one cell growth protein may still have an abundance of the other. The antibody targeting the other could therefore bring the drug-carrying antibody to cancer cells that would otherwise be difficult to reach.
The two antibodies also appeared to help pull the drug into the cancer cell. When they were joined together, more of the drug-carrying antibody was taken inside the cell, where the chemotherapy could be released.
Reaching Hard-to-Treat Tumors
In mice, the combined approach increased the amount of the drug-carrying antibody reaching tumors with very low levels of cell growth protein. In one model, tumor uptake increased more than threefold compared with the antibody targeting the cell growth protein alone. The treatment also slowed or stopped tumor growth more effectively than the same cancer drug given without the second antibody.
The effect was particularly striking in models of breast and pancreatic cancer with little or no cell growth protein. Conventional treatment produced limited responses in these tumors. The two-antibody approach significantly reduced tumor growth and extended survival in the mice.
The strategy also showed promise against tumors that had already become resistant to treatment. In mice whose tumors stopped responding to the drug targeting the first protein, the addition of the antibody targeting the second protein restored tumor control in some animals.
Beyond a Single Cancer
The significance of the approach goes beyond these two cell growth proteins. The underlying idea is to combine two existing targeting systems so that a cancer drug can reach tumors that are too varied for a single target.
The study also found that the same strategy could be adapted to different antibody pairs. The platform could be useful across tumors with different combinations of surface proteins.
The treatment still needs to be tested in people. The current results come from laboratory and mouse models, and further studies will be needed to determine its safety and effectiveness in patients. But the concept represents an important shift in targeted cancer treatment. Instead of asking whether a tumor has the right single target, future cancer therapies may be able to use multiple targets together to reach tumors that conventional antibody drugs cannot.