Targeting Survivin May Open New Avenues for Immunotherapy

Antibody-mediated, immunotherapeutic strategies that target survivin, a key cancer-related protein, may offer promising treatment approaches for a variety of cancers, according to a study published online in Clinical Cancer Research. Investigators at Roswell Park Comprehensive Cancer Center found that this commonly occurring molecule in cancer cells may be an attractive target for a broad range of immunotherapy approaches, including CAR-T (chimeric antigen receptor T-cell) therapy.

It has been known for some time that survivin is a protein present within the nucleus, cytoplasm, and mitochondria of the cell. Senior author Michael Ciesielski, PhD, from the Department of Neurosurgery at Roswell Park, Buffalo, New York, said it has been targeted in cancer cells by T-lymphocyte–mediated immunotherapeutic approaches. “We discovered that, contrary to previous understanding, survivin is also present on the cell membrane in a wide variety of cancer cells. Moreover, antibodies to survivin, which cannot ordinarily penetrate the intact cancer cell, inhibit tumor growth in vivo. These findings were quite surprising and contrary to established scientific dogma,” Ciesielski told Cancer Network.

Ciesielski and his team found that survivin is present on the outer cell membrane of a wide variety of cancer cell types, including both murine and human glioma cells. The researchers theorize that targeting the survivin protein may be more effective than standard therapy for some patients with glioblastoma. “Anti-survivin antibody-mediated therapies could be effective against a wide range of different cancers,” said lead study author Robert Fenstermaker, MD, Chair of Roswell Park’s Department of Neurosurgery. 

Survivin is highly expressed by many types of cancer, including many glioma, lung, pancreatic, breast, and neuroendocrine tumors, as well as some forms of multiple myeloma, lymphoma, and leukemia. Fenstermaker said since survivin is now known to be present on the outer surface of many different types of cancer cells, it may be possible to attack this protein through the use of targeted antibodies, antibody fragments, and CAR T cells. “The work identifies a new and potentially important target for cancer immunotherapy,” Dr. Fenstermaker told Cancer Network.

The researchers hope that this approach can be used to target both solid and liquid tumors, a finding that could help broaden the applications for CAR-T therapies generally. Currently, CAR-T therapies approved by the US Food and Drug Administration are limited to treatments for liquid/hematologic cancers.