Treating pancreatic cancer with personalized vaccine
Treatment of pancreatic ductal adenocarcinoma (PDAC), a common pancreatic cancer is a therapeutic challenge. It’s one of the deadliest types of cancer.
Despite modern treatment regimens and therapies, based on patients’ fitness, organ function, comorbidities, only about 12% of people diagnosed with this cancer survive five years after treatment.
In PDAC, the supporting structures of the cancer cells (stroma) is very dense and heterogeneous and could be the reason for resistance to most therapies. This could be due to lower levels of neo-antigens (protein that form on cancer cells when certain mutations occur in tumor DNA), the unique immunosuppressive tumor microenvironment (TME) and low levels of intra-tumoral infiltrating T-lymphocytes that can create the host to mount an attack on cancer.
Also whether pancreatic cancer cells produce neo-antigens—proteins that can be effectively targeted by the immune system—hasn’t been very clear so far.
Recent progress in the field of immunotherapy (drugs that help the body’s immune system attack tumors) and checkpoint inhibitors have shown little promise when it comes to PDAC.
An NIH-funded research team, led by Memorial Sloan Kettering Cancer Center (MSKCC) have been developing a personalized mRNA cancer-treatment vaccine. It is designed to help immune cells recognize specific neo-antigens on patients’ pancreatic cancer cells.
After surgery samples of study participants were sent for gene sequencing on the tumors, to find proteins that might trigger an immune response. This information was used to create a personalized mRNA vaccine for each patient. Each vaccine targeted up to 20 neo-antigens.
Customized vaccines were successfully created for 18 of the 19 study participants..
All patients received targeted drugs before vaccination. This drug, called an immune checkpoint inhibitor (works at the level of cell-cycle), prevents cancer cells from suppressing the immune system.
The vaccine was then given in nine doses over several months. After the first eight doses, study participants also started standard chemotherapy followed by a ninth booster dose.
The vaccines activated powerful immune cells, called T cells that could recognize the pancreatic cancer specific to the patient for 50% of the vaccinated patients.
To track the T cells made after vaccination, the research team developed a novel computational strategy. Their analysis showed that T cells that recognized the neo-antigens were not found in the blood before vaccination.
By a year and a half after treatment, the cancer had not returned in any of the people who had a strong T cell response to the vaccine. In contrast, among those whose immune systems didn’t respond to the vaccine, the cancer recurred within an average of just over a year. In one patient with a strong response, T cells produced by the vaccine even appeared to eliminate a small tumor that had spread to the liver. These results suggest that the T cells activated by the vaccines kept the pancreatic cancers in check.