Vaccines are mostly known as tools to prevent illness. But cancer vaccines can be a little different. While some work against viruses that can lead to cancer, like the vaccines that prevent human papillomavirus (HPV) or hepatitis B virus (HBV), most aim to use the immune system to attack cancer cells that already exist in the body. Cancer vaccines may be used to prevent metastasis.
Now researchers have evaluated the safety of personalized cancer vaccines and found that in patients with different cancers including lung and bladder cancers that have a high potential for recurrence; the vaccines showed a lot of therapeutic potential with no safety concerns. The results from the phase I trial were presented virtually at the American Association for Cancer Research (AACR) Annual Meeting 2021.
"While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments," said study author Thomas Marron, M.D., Ph.D., Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute. "Cancer vaccines...typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy."
The vaccines were developed by taking a sample of a patient's tumor, sequencing the DNA and RNA from those tumor cells, and the patient's germline DNA. The researchers identified a target specific to the tumor, and assessed whether the patient's immune system would recognize the target of the vaccine. A computational tool called OpenVax enabled the researchers to find the best targets and incorporate them into the personalized vaccines.
In the trial, each patient got standard treatment for their cancer (like surgery to remove a tumor or a bone marrow transplant), and then they received ten doses of a personalized vaccine and an adjuvant over six months. The adjuvant acts as an immunostimulant, which promotes the immune response; it's called ICLC and is "a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumor neoantigens," said study author Nina Bhardwaj, M.D., Ph.D., Director of the Immunotherapy Program and the Ward-Coleman Chair in Cancer Research at The Tisch Cancer Institute at Mount Sinai.
"Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread," said Bhardwaj. "We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal - typically microscopic - residual disease. Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types."
There were thirteen patients in the trial, who all had a high chance of disease relapse. Ten had solid tumors and three had multiple myeloma and all got a personalized vaccine. After 880 days, four had no evidence of cancer, four were getting additional therapeutics, one had elected to stop the trial, and four had died, but not from the vaccine. The vaccine was safe; one-third of patients had only minor side effects at the injection site. One patient's immune system began to respond to their cancer after the vaccine, while two responded well to immunotherapy after they got the vaccine.
There are five more phase I trials planned now for other types of cancer.
Sources: AAAS/Eurekalert! via The Mount Sinai Hospital / Mount Sinai School of Medicine, American Association for Cancer Research
