Immunotherapy is a method of fighting cancer that revolves around empowering the immune system to reach its full cancer-killing potential. But tumor cells are constantly finding ways to resist and retaliate, so counterattacks are always necessary.
A growing tumor generates its own system of blood vessels that flood cancer cells with oxygen and nutrients. In addition to providing nourishment, these vessels block the arrival of T cells either naturally sent by the immune system or sent as a result of an immunotherapy to boost T cell activity. Tumors rely on two key proteins to stimulate the growth of their blood vessel network and to keep T cells at bay: VEGFA and ANGPT2.
A new approach designed by experts from the Ecole Polytechnique Federale De Lausanne (EPFL) in Switzerland may be the answer: an antibody called A2V that simultaneously blocks VEGFA and ANGPT2 and metastasis.
"A2V not only regressed most of the tumor blood vessels, but also reversed the aberrant features of those that had remained, making them similar to normal blood vessels and more permissive to the arrival of anti-tumoral T cells,” explained study leader Michele De Palma.
By preventing tumors from reaping the benefits of their blood vessel system, A2V offers a new solution for treating many different types of cancer. However, the EPFL study showed that tumors were quick to answer back with a solution of their own: expression of protein PD-L1 that binds to PD-1 on the surface of T cells to prevent T cells from attacking. Thankfully, scientists have already developed antibodies that serve as checkpoint inhibitors to counter the PD-L1/PD-1 inhibition of T cells.
“Certain anti-angiogenic drugs, namely ANGPT2 inhibitors, have more profound effects on tumors than initially thought,” De Palma explained. “Besides targeting the blood vessels, they also help initiate anti-tumoral immune responses, which can be reinforced by immune checkpoint blockade.”
Based on De Palma’s findings, it seems that scientists are just unveiling the beginning of the potential benefits of applying the A2V antibody. Future studies will illustrate just how valuable this new approach will be for fighting cancer.
The present study was published in the journal Science Translational Medicine. For more on cancer immunotherapy, check out the video below: