Tuesday, April 05, 2022

Tetanus Immunity Protects Mice Against Pancreatic Cancer

Good news! This seems to be an interesting approach! Cancer is history soon!

"Researchers have leveraged childhood immunity to tetanus in order to target treatment-resistant pancreatic cancer, according to a new study published this week (March 23) in Science Translational Medicine. Using an inert, nontoxic species of Listeria bacteria, scientists were able to deliver benign tetanus proteins into pancreatic tumor cells in mice, thereby flagging them as foreign to circulating memory immune cells. Following the treatment, both the original tumor and those that had metastasized shrank significantly, and the mice lived longer as a result. ...
Pancreatic cancer is difficult to treat for several reasons. The cancerous cells often lack the mutational vulnerabilities exploited by current pharmaceutical therapies. Tumors also often grow and metastasize before the onset of symptoms. And as they grow, they secrete molecules that dampen the local immune response while also coating themselves in thick, fibrous myeloid-derived cells that physically shield the tumor. “Pancreas cancer goes cloaked,” ... As a result, only 10 percent of patients live for more than five years after diagnosis. ...
Listeria, the bacteria behind most cases of food poisoning, as a means to circumvent pancreatic cancer’s many tricks. Listeria preferentially infects cancerous and tumor-associated cells, and the form ... used was genetically modified to bear proteins from the bacteria that causes tetanus. Because most people are immunized against tetanus as children, the body’s memory T cells continue to recognize tetanus antigens throughout life, even if cancer-spotting T cells fail to recognize pancreatic cancer. ...
Moving forward, the researchers plan to test the new technique in humans. ... a patent for the therapy has already been licensed to New York-based biotech company Loki Therapeutics ..."

From the abstract:
"Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT856-1313) into PDAC tumor cells by attenuated Listeria monocytogenes. This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria-TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria-TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria-TT + GEM–treated mice demonstrated a CD4 T cell–mediated reduction in tumor burden. ... Listeria-TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. ..."

Tetanus Immunity Protects Mice Against Pancreatic Cancer | The Scientist Magazine® Because most people are vaccinated against tetanus as children, delivering benign bacteria carrying a tetanus antigen into pancreatic tumors makes them visible to memory cells in the immune system, researchers report.

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