Scientists from the Cancer Vaccine Collaborative (CVC) have discovered that the cancer-specific protein, SSX-2, induces a spontaneous immunological reaction against cancer cells in melanoma patients, offering a new target for the development of a therapeutic melanoma vaccine. SSX-2 is the prototype of the SSX family, and is part of a larger group of proteins known as cancer/testis (CT) antigens. CT proteins are expressed in cancer cells and on normal testes, but the immune system recognizes CT antigens only when they are present on cancer cells. This exquisite immunological specificity for cancer, but not normal, cells has drawn many scientists and clinicians to investigate vaccines against CT antigens as cancer therapies.
“SSX-2 is a particularly good target for a cancer vaccine,” says Dr. Danila Valmori, an Assistant Member of the Ludwig Institute for Cancer Research (LICR), and the senior author of the study. “We found that patients are mounting their own immunological responses against cancer cells expressing SSX-2, and although these spontaneously occurring immunological responses are apparently not sufficient for stopping tumor growth, possibly because they develop late in the disease progression, we think that a vaccine that stimulates and amplifies this naturally-occurring attack will have a good chance of giving a clinical response.”
The CVC, which was established by the Cancer Research Institute (CRI) and LICR, had previously reported the detection of SSX-2-specific CD8+ T cells and antibodies in patients with melanoma. However, in the report published today in the Journal of Clinical Investigation, they describe the discovery of SSX-2-specific CD4+ T cells, the final member of the immunological triumvirate. Work is underway to characterize the immunogenicity of the other SSX family members, which were originally identified by LICR researchers in New York.
“We believe that for a cancer vaccine to be effective, you really need to be able to induce, and monitor, the activation of all three components of the immune system,” explains Dr. Jill O’Donnell-Tormey, the Executive Director of CRI. “So with this important preclinical work complete, we can now begin early-phase trials of SSX-2 based vaccines to work out variables such as the best vaccine composition, the best dose, the best delivery methods, and so on. And because we know how to monitor the SSX-2-specific responses of T cells and antibodies, we can speed the refinement of an SSX-2 vaccine by using standardized monitoring, and investigating several vaccine variables in parallel trials at different CVC Centers.”
The first early-phase clinical trial, which will assess the safety and dose profiles of an SSX-2 peptide-based vaccine, is scheduled to begin this year at the CVC Clinical Trials Center in Zürich, Switzerland.