Authored by: George M. Pikler, M.D., Ph.D., FACP
The discovery of cancer immune checkpoints and the success of checkpoint inhibitors, as well as the advances in technology to generate genetically modified immune cells opened a brand-new chapter in the war against cancer. The use of vaccines to prevent cancer from evolving and becoming resistant to treatment, has shown exciting results.
The focus of treatment has shifted from the tumor itself to the host’s immune system, to mobilize immune cells to recognize and eventually eliminate the cancer cells. Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Despite the unprecedented durable response rates observed with its use, many patients do not benefit from the treatment (primary resistance), and some responders relapse after a period of response (acquired resistance).
A team of researchers1 affiliated with multiple institutions in the U.S. and one in Japan has developed a new type of vaccine that helps the immune system destroy cancerous tumors by overcoming their defense system. While investigating the use of a cancer- killing virus in clinical trials, they observed, as they had also seen in mice, that although some patients initially responded to the treatment, their tumors soon became resistant. Virus treatment caused a mutation within the cancer cells, in a gene called CDSE1, which usually protects against viruses by slowing their replication.
The mutated CDSE1 protein, produced by the CDSE1 gene, created a unique antigen – a structure recognized by the immune system as a target – which the researchers used to develop a vaccine. They exploited the tumor’s defense mechanism by vaccinating against the mutated cells. This they called a ‘trap and ambush’ approach; forcing a tumor to evolve in a specific way as a defense mechanism against treatment and ambushing it by vaccinating against this defense mechanism. This vaccine triggers the immune system to destroy the drug resistant tumor cells, preventing the cancer from further evolving.
Combining frontline virotherapy with escape-targeting immunotherapy will be applicable across multiple therapies which drive tumor mutation/evolution and simultaneously generate novel, targetable immunopeptidomes associated with acquired treatment resistance.
1Timothy Kottke, et al. Nature Communications (2021) 12:1930.
George M.Pikler, M.D., Ph.D., FACP
Lead Oncology Advocate N1X10
Dr. Pikler graduated summa cum laude from the Central University of Ecuador School of Medicine in 1968. His postdoctoral training included an internship in internal medicine at Greater Baltimore Medical Center in Baltimore, MD, a residency in internal medicine and a doctoral degree in molecular medicine at the Mayo Clinic in Rochester, MN. The American Cancer Society awarded him a fellowship in medical oncology and hematology at M.D. Anderson & Tumor Institute in Houston, TX.
With training certifications in internal medicine and oncology, Dr. Pikler and his family moved to Tulsa, OK where he established and was the President of Cancer Specialists, Inc, a boutique oncology-hematology clinical research private practice. In addition, he was the chief of the oncology at Hillcrest Medical Center, a teaching hospital for 20 years and associate professor of medicine, oncology-hematology at the University of Oklahoma, Tulsa Medical College. He was one of the founders of the Southern Association of Oncology Practices and subsequently the National Medical Director for the International Oncology Network, AmerisourceBergen’s Oncology Division.