Next-generation cancer immunotherapy enters clinical trials


Next-generation cancer immunotherapy enters clinical trials

Scientists have developed a new experimental drug that aims to use the body’s immune system in a response to cancer, which is now entering the early stages of clinical trials.

The investigational drug was developed by Cancer Research UK scientists and targets suppressive ‘regulatory’ immune cells within a tumor, significantly improving long-term survival in animal models even when used without other drugs. The drug’s potent effect has been seen in multiple mouse models of cancer, with some models showing a response close to 100%.

If this clinical trial, which aims to determine the safety of the drug in people with advanced cancer, and larger follow-up studies are successful, it could lead to a new immunotherapy treatment for people with high numbers of a certain cell type. immune system found in cancers such as melanoma, some lung cancers and head and neck cancer.

The study was published in the journal Nature.

How does the drug work?

Regulatory T lymphocytes, or “Tregs,” usually act as brakes on our immune system, preventing it from becoming hyperactive, and previous work has shown that these cells are often found in high numbers in tumors. They are thought to prevent other immune cells from eradicating the cancer. A hallmark of Treg immune cells is a protein called CD25, which is present in large quantities on the surface of cells.

Drugs that target the CD25 protein have previously been used to kill regulatory T lymphocytes to try to release these immune system dampening brakes, however these drugs have been ineffective. This new study reveals why they have not been effective so far, leading to the development of the new immunotherapy drug.

Led by Professor Sergio Quezada and Professor Karl Peggs, the Cancer Research UK team found that previous CD25 drugs inadvertently affected tumor ‘effector’ T cells that kill cancer, reducing the effectiveness of their immune response against cancer. disease.

Professor Sergio Quezada, co-lead author of University College London, said: “For many years it has been a complex mystery; because targeting CD25 with other drugs was not as effective as expected. Now, going back to basic biology and discovering the mechanism behind this protein, we found that targeting CD25 was absolutely the right approach, but we needed to target a different part of the protein. “

The team was able to invent the new drug, an antibody that binds to a different part of the CD25 protein than other currently available drugs.

Professor Sergio Quezada said: “This drug not only kills the regulatory immune cells that dampen the immune response to cancer, but also activates the immune cells that kill cancer. This two-pronged approach is a huge opportunity to significantly alter the tumor network of cells in and around the tumor, so that they no longer protect the tumor cells, but start turning against the tumor. “

Professor Karen Vousden, chief cancer research scientist in the UK, said: ‘This is a prime example of how studying cancer in the laboratory can lead directly to experimental treatments for people with the disease. Therapies that activate an immune response against cancer have already been a game changer for many types of cancer, but they only work for a minority of patients. One approach to trying to make them more effective has been to try to target immune cells called regulatory T cells, which normally limit the immune response. However, attempts to do so have not been successful.

“In this study, UCL Cancer Research UK scientists figured out why these previous attempts failed and, in doing so, invented a new antibody devoid of these additional unwanted activities and demonstrated that it produces potent anticancer responses in mice. Now. is being tested in clinical trials against several types of cancer. “

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