An Unlikely Pair: New Pancreatic Cancer Vaccine Utilizes Immunity from Tetanus
An article published this week in Science Translational Medicine has provided a possible solution for the daunting task of treating patients with pancreatic cancer. Researchers at Albert Einstein College of Medicine have cleverly developed a vaccine for pancreatic cancer by using the adaptive immunity already present in nearly all of the global population. The novel approach could mark a turning point in the long road to pancreatic cancer treatments.
According to the National Cancer Institute, pancreatic cancer affected over 60,000 patients in the U.S. in 2021, with over 48,000 mortalities. The disease has a morbid 10.8% five-year survival rate after diagnosis. While many drugs and biologics aim to treat pancreatic cancer, none have been hailed a miracle drug, much less a cure. The nature of pancreatic cancer allows diseased cells to escape immune defenses, as the body does not identify those cells or tumors as foreign.
Within the college’s Albert Einstein Cancer Center, which holds a prestigious membership to the National Cancer Institute, Claudia Gravekamp, Ph.D. and a team of experts took on the challenge to develop a way to hijack a patient’s already-existing immunity to work against pancreatic cancer. The fruit of their efforts is described in the article.
The article, titled "Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice," describes preclinical research using the new formulation to inject pancreatic cancer mice showed astonishing efficacy. The mice displayed a mean 80% reduction in tumor size and an 87% reduction of cancer metastases. Low doses of an immune-suppressing chemotherapeutic, gemcitabine, were also used during treatment.
When fully inoculated with a vaccine, the human body is exposed to small fragments of the disease. In response to the disease exposure, the body develops antibodies as a way to prepare for any future exposure. These antibodies act as a biological memory bank called adaptive immunity. Knowledge of this memory bank, coupled with the awareness that most of the world has been vaccinated against tetanus allowed them to elicit a response from pancreatic cancer cells by infecting them with the bacteria that deliver tetanus toxin.
Using Listeria monocytogenes bacteria as an infectious agent, the team integrated DNA of the tetanus toxin to formulate a new injectable vaccine. The bacterium is fairly weak, breaking down as the tetanus toxin infiltrates tumor regions and encourages memory T-cells to activate. In summation, the immune system’s T-cells become retrained to identify pancreatic cancer cells and attack them, just as they had been trained to identify and attack tetanus.
In addition to performing cutting-edge research as an associate professor of microbiology and immunology at Einstein, Dr. Gravekamp is also co-founder and principal scientist of Loki Therapeutics. Loki has been granted licensing of this biotechnology and intends to eventually bring it to commercialization.
According to a 2020 World Health Organization report, 83% of the global population has been immunized against tetanus. While not completely eliminated, the infectious disease has only been seen sparingly, with cases mostly occurring in tropical climates and countries with underdeveloped vaccination programs. If research continues to show promising results, researchers at Loki Therapeutics hope to investigate how to take advantage of this high percentage to formulate treatments for additional forms of cancer.