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.

One hundred six poster presentations and four oral presentations capped off new research that was conducted by students at the Icahn School of Medicine at Mount Sinai and featured at Mount Sinai’s Fourth Annual Karen Zier, PhD, Medical Student Research Day, held over Zoom in March.

Participating in Research Day fulfills one of the medical school’s graduation requirements. Eighty percent of the presenters each year are in their second year of medical school.

“Medical Student Research Day is a showcase and an opportunity for students to share the research and scholarship they have done with their mentors with the Mount Sinai community,” says Mary Rojas, PhD, Director of Icahn Mount Sinai’s Medical Student Research Office, and Associate Professor of Medical Education. “It is an early snapshot of the students’ accomplishments.”

Dr. Rojas says that by the time they graduate, more than half of Mount Sinai’s students will have published in peer-reviewed journals. The Class of 2021 has already published more than 400 peer-reviewed articles.

The event exemplifies Mount Sinai’s commitment to fostering biomedical research and introduces students to the intellectual rigors, skills, and collaboration that lead to incremental findings and life-changing discoveries.

Under the mentorship of Tanvir Choudhri, MD, Associate Professor of Neurosurgery, at Icahn Mount Sinai, second-year student Zachary Spiera found that the use of non-steroidal anti-inflammatories (NSAIDs), which diminish inflammation, does not make users more susceptible to concussions and does not worsen their outcomes. This was a subject he had wondered about because he and his teammates had plied themselves with NSAIDs while playing basketball and soccer in high school and middle school.

Before launching his own research, Mr. Spiera searched through medical literature, but could not find an answer. “As a student you look up to the medical community and think there are going to be answers to your questions,” he says. “Then you see something that hasn’t been figured out yet.” He is first author on a study about this subject that was recently accepted for publication in the Journal of Neurosurgery: Pediatrics.

This spring, Jordyn Feingold will receive a joint MD and Master of Science in Clinical Research, before continuing at Mount Sinai for her residency in Psychiatry. At Research Day, she presented her work on the psychological impact of the COVID-19 pandemic on 2,579 front-line health care workers at The Mount Sinai Hospital. She and her mentor, Jonathan Ripp, MD, MPH, Dean for Well-being and Resilience and Professor of Medicine (General Internal Medicine, and Geriatrics and Palliative Medicine) recently published their findings in the journal Chronic Stress.

One of the study’s key takeaways, Ms. Feingold says, was the high prevalence—39 percent—of COVID-19-related post-traumatic stress disorder, major depressive disorder, or generalized anxiety disorder that existed among the hospital’s front-line health care workers at the peak of the pandemic last year. The “greatest driver of those symptoms was being burned out, which is significant,” she says, “because it was happening well before COVID-19 and it is something that can be addressed.” Her research also found “the greatest modifiable protective factor was feeling supported by hospital leadership.”

The COVID-19 pandemic provided a springboard for student research by others, including second-year students Cynthia Luo, Alexander Kalicki, and Kate Moody, who also presented abstracts of their studies on Research Day.

Ms. Luo studied resilience among her fellow medical students during the pandemic under the mentorship of Craig Katz, MD, Clinical Professor of Psychiatry, Global Health, and Medical Education, at Icahn Mount Sinai. She divided students into two groups: those who responded to a survey by saying the COVID-19 pandemic had been their most traumatic life event, and those who responded by saying they had experienced earlier life traumas, such as the loss or illness of a loved one. Ms. Luo then measured their responses on a resilience scale that was created at Mount Sinai. “Students who indicated a non-COVID-19 impactful life event had significantly higher resilience than those who indicated COVID-19,” says Ms. Luo. “To me that demonstrates that having prior stressful life experiences was, in some ways, protective for managing COVID stress. Potentially, these experiences helped students grow and develop their resilience behaviors before COVID-19.” Ms. Luo plans to finish compiling her research and submitting it for publication in the coming months.

Mr. Kalicki and Ms. Moody are co-authors on a study that was just accepted by the Journal of the American Geriatrics Society (JAGS), which examined the barriers to video-based telehealth access that older homebound adults faced during the pandemic. Mr. Kalicki worked as a software engineer before entering medical school and says his passion for using technology to improve health care delivery led him to pursue the project under the mentorship of Peter Gliatto, MD, Professor of Medicine (General Internal Medicine), Geriatrics and Palliative Medicine, and Medical Education at Icahn Mount Sinai. Katherine Ornstein, PhD, MPH, Associate Professor, Geriatrics and Palliative Medicine, also served as the students’ mentor.

Ms. Moody says she was drawn to the subjects of process improvement and providing a high level of health care to a population that is difficult to access. Both students helped design a survey that was completed by physicians in the Mount Sinai Visiting Doctors Program and conducted the data analysis for the study. They also created a data collection sheet for Mount Sinai’s Epic electronic health record system to systematically record information about patients’ previous telehealth use, as well as structural barriers patients may face, such as access to the internet or the capacity to pay for cellular data. The students hope that a better understanding of these barriers will help inform future interventions that are designed to reach patients with limited access to care.