In the fight against cancer, success demands precise intelligence and determined soldiers. However, the tumor microenvironment places these elite immune cells at a disadvantage. Cancerous growths induce exhaustion in T cells, while the dendritic cells—essential for activating these T cells and providing critical information—are in short supply. This imbalance helps explain why immunotherapy, a promising new approach that enables the body’s immune system to target and contain cancerous growths, proves effective in some cases but falls short for most patients.
Now, researchers of Israel’s Weizmann Institute of Science (WIS) and their colleagues from the United States have developed an antibody-based treatment that enables T cells to connect with dendritic cells and unleash a potent assault on cancerous growths. The results, published in the journal Cell Reports, show that the antibody significantly slowed tumor growth and, in some cases, caused complete recovery in mouse models of breast cancer.
Using an antibody that blocks the formation of molecular bridges, the researchers linked T cells with dendritic cells near the tumor. This increased the number of such cellular pairs around the growth and in the adjacent lymph nodes, allowing the T cells to receive the required “intel” from dendritic cells. These T cells then accelerated the attack on cancerous growths, halting tumor progression in mice.
The researchers also tested the effect of an existing treatment, which uses antibodies to block PD-1, a protein widespread in the tumor microenvironment that can attach to T cells and cause them to enter a state of exhaustion. However, their experiments revealed that this type of treatment fails to stimulate a robust immune response in most cancer patients because the relevant population of dendritic cells is very small in most tumors.
By contrast, the scientists’ new antibody uses two arms – each targeting an entirely different cell type. One arm binds to T cells, inhibiting PD-1’s interaction with them, just as existing treatments do; the other recruits dendritic cells from the rare population present in most cancerous growths and is necessary for activating T cells. When this antibody was given twice a week to mice with developing breast cancer, it substantially slowed their tumor growth and, in some cases, led to full recovery.
