The image of this Phase 1 trial shows the progress of one patient who began to mount a robust immune response to their cancer six months after receiving the full 10 dose-regimen of Mount Sinai’s experimental cancer vaccine. (T cells are represented by black dots, as seen in the bottom row.)
The first personalized cancer vaccine administered to patients prior to evidence of spread but after surgery or a stem cell transplant, was shown to be safe, well tolerated, and potentially beneficial in preventing disease recurrence in a phase 1 clinical trial at The Tisch Cancer Institute of the Mount Sinai Health System.
The results of the trial were presented virtually, in April, at the American Association for Cancer Research (AACR) Annual Meeting and generated excitement among attendees. It was the first time a personalized vaccine of this sort had been given to patients with a variety of cancers—including lung, breast, ovarian, and head and neck cancers as well as multiple myeloma, a disease of the white blood cells. Prior to receiving the vaccine, the patients either had surgery or an autologous stem cell transplant as a standard-of-care treatment. After an average follow-up of 880 days, 4 of the 13 patients in the trial had no evidence of disease.
Thomas Marron, MD, PhD
“Most of the patients in our study had well over a 50 percent chance of the cancer coming back,” says trial co-leader Thomas Marron, MD, PhD, Assistant Professor of Medicine (Hematology and Medical Oncology), and Director of The Tisch Cancer Institute’s Early Phase Trial Unit. “The No. 1 thing we were interested in was, did we successfully teach the patient’s T cells, their immune cells, what to look out for and what to kill in case there were microscopic pieces of the tumors that remained in the body? Hopefully, if the patient does have residual disease, those T cells can hunt it down and kill it.”
Immunotherapies are usually given after the patient’s cancer has already metastasized or spread to other parts of the body. But Mount Sinai administered its personalized vaccine before there was evidence of spread, so the vaccine could teach the body’s immune cells what to be on the lookout for in case remaining tumor cells were still circulating after surgery or stem cell transplant.
Another unique aspect of the trial was that each patient’s genetic information, including their normal DNA as well as their tumor’s DNA and RNA, were sequenced and run through OpenVax, Mount Sinai’s proprietary, computer program.
OpenVax compared the genetic information from the patient and the tumor to define which mutations, or changes, were unique to the tumor, and then identified 10 “foreign” proteins in each patient’s tumor that the patient would most likely develop an immune response to. A personalized vaccine for each patient was then created from synthetic versions of each of those 10 proteins in Mount Sinai’s Vaccine and Cell Therapy Laboratory, a highly specialized unit that meets the manufacturing standards of the U.S. Food and Drug Administration. The laboratory is run by the trial’s senior leader, Nina Bhardwaj, MD, PhD, Ward-Coleman Chair in Cancer Research, and Director of Immunotherapy at Icahn Mount Sinai.
Since the cost of developing each of these personalized vaccines is extremely high, it is unlikely that there will be a phase 2 of this particular trial, according to Dr. Marron. The goal of the trial “really is about informing future novel therapies,” he says. “Ideally, we will be able to get to the point where we do a biopsy and send it off to a lab and receive a vaccine, but that is very difficult to do now and very expensive. As the technology improves it may become possible.”
Nina Bhardwaj, MD, PhD
During their next phase of research, the Mount Sinai team plans to develop vaccines that can be administered to groups of patients who have the same cancerous mutations, instead of focusing on each patient’s unique DNA.
This research is being informed by Dr. Bhardwaj, who was the senior author of a paper in the December 10, 2020, issue of the journal Cell, which found that similar mutations appeared in a subset of patients with stomach, colon, and endometrial cancers.
“I’m looking forward to creating what we call ‘shared neoantigen vaccines,’” Dr. Marron adds. “This is based on our understanding that certain mutations exist in a high percentage of lung cancers, pancreatic cancers, colon cancers, and other types of cancer. If we were able to make a vaccine that covers, say, 100 different mutations, we would have a vaccine that could help a majority of cancer patients in the world.”
Currently, Dr. Marron and other top researchers at Mount Sinai are making inroads in an area of cancer vaccine development called in situ or “at the site of” vaccines, with at least eight early trials now under way. These vaccines are being administered to patients whose cancerous tumors have metastasized following their first round of standard-of-care treatment, such as surgery, chemotherapy, or radiation. Patients receive an injection directly into one of their tumors of an adjuvant that revs up the immune system, which instructs the immune system to find and kill other pieces of the tumor that may remain in the body.