The clinical trial, which has not yet been peer-reviewed, found that 82% of patients had a reduction in PSA levels and half had a decrease in their tumor.
A new immunotherapy drug has demonstrated promising results in a recent clinical trial for prostate cancer. The drug, called VIR-5500, is a “masked T-cell engager.” This type of immunotherapy activates our own immune arsenal to fight cancer.
In , which is still ongoing and has not been peer-reviewed, patients with advanced prostate cancer who have not responded to other treatments received FOR-5500.
Initial results showed that in patients who received the highest doses, 82% showed a reduction of PSA (prostate specific antigen) levels – a commonly used indicator for prostate cancer.
Surprisingly, almost half of the patients in this group also had a reduction in the tumorboth at the site of the primary tumor and in metastatic tumors (tumors that have spread from the prostate to other parts of the body).
Cancer cells have mechanisms to escape elimination by our immune system. But immunotherapies increase the capacity of our immune system to fight cancer. They do so by combating these evasion strategies.
Several immunotherapies have demonstrated phenomenal success in recent years. However, many types of cancer, such as prostate cancer, remain difficult to treathighlighting the need for more effective immunotherapies.
T-cell engagers are a specific type of immunotherapy that works by docking immune cells, called T cells, and cancer cells, interacting with molecules on the surface of both cell types. This forced proximity causes T cells to produce toxic chemicals that destroy cancer and generate a cascade of inflammatory processes that promote cancer destruction.
Currently, there are more than 200 different T cell engagersmany of which are in clinical trials to treat a variety of tumors, including multiple myeloma, leukemia, and lung cancer.
T cell engagers
T cell engagers are not just being tested for cancer. They can also help treat other viral illnesses, such as hepatitis B, which can cause chronic infection. Just like cancer, the virus can evade our immune responses, but T cell engagers can promote more effective elimination of virus-infected cells.
Despite the great promise surrounding T-cell engagers, the vigorous inflammation they trigger may also be a double-edged sword. In some cases, it can cause a serious inflammatory condition called cytokine release syndrome.
Cytokines are messenger proteins released by cells that can drive inflammation. Normally, its release is strictly controlled, but in cytokine release syndromethe response is excessive and uncontrolled. This can lead to multiple organ failure with potentially fatal consequences.
Similar toxic inflammatory side effects may be seen with other immunotherapies. The condition is likely to be caused by powerful and acute activation of an immune response.
This is why T cell engagers and other immunotherapy drugs need to be improved to ensure that its effects are less toxic.
One way to do this involves producing versions of immunotherapies that are inactive, but can be activated once inside tumors.
This is done by coating the medicine with a “mask” that prevents it from interacting with both T cells and cancer cells. When the drug enters tumors, molecules abundant in the cancer can break down this mask, allowing the drug to medicine interacts with its target cells. VIR-5500, the drug used in this recent promising prostate cancer clinical trial, is one of many new masked T-cell engagers.
Thus, masking creates an effective medicine that may also be safer. Tumor-specific activation must restrict the antitumor inflammatory response to the interior of the tumor, preventing widespread inflammation.
It may also allow T cell engagers to be more selective toward cancer cells, since some of their targets can also be expressed by normal healthy cells. This could, simultaneously, reduce toxicity and improve antitumor potency.
An additional benefit of masked immunotherapies is that the conversion of inactive to active medication in the body takes time. This changes the way the medicine is dosed to patients.
In clinical practice, T cell engagers are often administered in small doseswhich subsequently need to be increased to avoid acute immunological hyperactivation. However, the mask would allow the medicine to be released more slowly, making administration simpler and safer. The mask itself can also prevent the degradation of medications by the body, prolonging their half-life.
An important finding in this recent clinical trial for prostate cancer was that the majority of patients receiving the highest doses of VIR-5500 experienced only mild inflammatory side effects. Considering the known toxicity associated with T cell engagers, this is an encouraging finding, suggesting that masking is working to reduce the risks of excessive inflammation.
If future research proves that masking T cell engagers results in safer and more effective medicines, we could expand their applications. They can be combined with more traditional oncological therapiessuch as chemotherapy or radiotherapy, which may prove to be even more effective in eliminating cancer.
Other masked T cell engagers have also demonstrated early promising clinical results in prostate cancer, and clinical trials have been initiated in several other types of cancerincluding pancreatic, colorectal and lung cancer.
As these trials are still ongoing, it is too early to know the full extent of clinical success. Furthermore, initial trials only test a small number of patients. The data has also not yet been subjected to peer review and has only been presented at oncology conferences.
Still, the initial results represent great hope for treating cancers that have proven difficult to treat with other immunotherapies.
