Antibodies Gain the Upper Hand Against Sly Tumors
Tumors use ingenious approaches to stay just out of reach of immune cells on patrol and avoid detection. For instance, cancer cells at the periphery of the tumor have been shown to secrete a cocktail of chemicals that creates an impenetrable barrier to immune cells. By suppressing the immune system, these tumor factors interfere with antigen-presenting cells such as macrophages and block the production of tumor-specific T lymphocytes. Beyond the reach of the immune patrol, tumor cells continue to multiply uncontrollably.
“Clinical trials with anti-OX40 antibodies have shown that the body can tolerate these drugs but unfortunately have also shown disappointing clinical responses.”
Scientists have developed several therapeutic countermeasures to overcome this tumor-induced immune suppression-treatments that, at least in theory, bear tremendous potential. Unfortunately, when it comes to real-world clinical outcomes, many of these immunotherapies have missed the mark. For instance, some studies show that more than half of patients fail to respond to checkpoint blockade therapy as a means of overriding tumors’ immune suppression.
Now, cancer immunologists from the University of Southampton have added a promising new immunotherapy that’s destined to boost oncologists’ tumor-fighting arsenal: an antibody that targets an immune molecule called OX40. The results were published in the Journal for Immunotherapy of Cancer.
OX40 is predominantly expressed in a subset of T cells called Treg cells-specialized immune cells that regulate immune activity. Tregs have been observed to be prevalent around the outer border of tumor tissues, suppressing immune activity in this tumor microenvironment. The new antibody therapy binds specifically to OX40, inactivating Tregs and allowing other immune effectors to enter the scene and begin tumor destruction.
Antibody and vaccine experts Mark Cragg and Jane Willoughby, who led the study, also found that by swapping the antibody isotype, or the region which determines the antibody’s effector function, their new therapy was a potent activator of killer T cells. This triggered a powerful and sustained immune…