Mount Sinai Creates First Experimental Personalized Vaccine for a Variety of Cancers

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.

Compassion and Connection: Caring for Patients in a Time of Need


Patient Experience Week, observed Monday, April 26, through Friday, April 30, honors the people who improve the patient experience every day and celebrates their accomplishments.

From nurses and physicians to support staff and executive professionals, all Mount Sinai employees are part of the patient experience.

This year Mount Sinai is recognizing how employees connected with patients through compassion during COVID-19. In this video, you can see how in many different ways, teams across many Mount Sinai locations—both clinical and non-clinical, remote and in-person—rose to the occasion, moved past barriers, showed compassion, and innovated to effectively care for patients in a time of need.

Watch Mount Sinai Brooklyn

Watch Mount Sinai West

Watch Mount Sinai Beth Israel

Watch NYEE

Watch Mount Sinai Queens

Mount Sinai Doctors

Mount Sinai South Nassau

Mount Sinai Morningside

The Mount Sinai Hospital

Watch the slideshow of employees throughout the Mount Sinai Health System

 

Pregnancy and Antidepressants: Should You Avoid Taking Them?

Approximately half of women who use antidepressants before pregnancy decide to discontinue use either before or during pregnancy due to concerns about the negative consequences for their child.

Those who are pregnant or who may be thinking of getting pregnant may wonder if taking antidepressants could affect the heath of the child. New research from Mount Sinai offers some potentially important findings and shows that the underlying mental health of the parents is more of a concern than the medication itself.

The study shows that while there is a link between maternal antidepressant use during pregnancy and affective disorders in the child later in life, the link also exists between paternal antidepressant use during pregnancy and child mental health.

The data suggest the observed link is most likely due to the underlying mental illness of the parents rather than any “intrauterine effect,” which means any effect the medication could have on the fetus developing inside the uterus. These affective disorders include depression and anxiety.

“Our study does not provide evidence for a causal relationship between in-utero exposure to antidepressants and affective disorders in the child,” says Anna-Sophie Rommel, PhD, an instructor in the Department of Psychiatry at Icahn Mount Sinai and first author of the paper. “So, while other long-term effects of intrauterine exposure to antidepressants remain to be investigated, our work supports antidepressant continuation for women who would like to continue taking their medication, for example because of severe symptoms or a high risk of relapse. It is important to note that untreated psychiatric illness during pregnancy can also have negative consequences on the health and development of the child. Women and their health care providers should carefully weigh all of the treatment options and jointly decide on the best course of action.”

Anna-Sophie Rommel, PhD

Approximately half of women who use antidepressants before pregnancy decide to discontinue use either before or during pregnancy due to concerns about the negative consequences for their child, according to Dr. Rommel, who is also an expert in epidemiology and has been studying how the COVID-19 pandemic disproportionately affects pregnant women in underserved communities.

Major depressive disorder is highly prevalent, with one in five people experiencing an episode at some point in their life, and is almost twice as common in women than in men. Antidepressants are usually given as a first-line treatment, including during pregnancy, either to prevent the recurrence of depression, or as acute treatment in newly depressed patients. Antidepressant use during pregnancy is widespread and since antidepressants cross the placenta and the blood-brain barrier, concern exists about potential long-term effects of intrauterine antidepressant exposure in the unborn child.

Using the Danish National Registers to follow more than 42,000 babies born during 1998-2011 for up to 18 years, researchers at the Icahn School of Medicine at Mount Sinai investigated whether exposure to antidepressants in the womb would increase the risk of developing affective disorder like depression and anxiety in the child.

In a study published April 5 in Neuropsychopharmacology, the scientists found that children whose mothers continued antidepressants during pregnancy had a higher risk of affective disorders than children whose mothers stopped taking antidepressants before pregnancy.

However, to understand whether the underlying disorder for which the antidepressant was given or the medication itself was linked to the child’s risk of developing an affective disorder, they also studied the effect of paternal antidepressant use during pregnancy and similarly, found that children of fathers who took antidepressants throughout pregnancy had a higher risk for affective disorders. Thus, the research team speculates that rather than being an intrauterine effect, the observed link is most likely due to the parental mental illness underlying the antidepressant use.

Saving Baby Nathaniel: As the Nation Went Into Lockdown Mount Sinai’s Liver Transplant Team Went Into Overdrive

Image of jaundiced 6-month-old Nathaniel in hospital prior to transplant

Prior to his transplant surgery, Nathaniel Capelo was severely jaundiced. He required continuous blood transfusions and his belly had to be drained of fluid every other day.

On March 18, 2020, the anguished parents of 6-month-old Nathaniel Capelo sat in his hospital room at The Mount Sinai Hospital facing the grim reality that he would die within days if he did not receive a new liver. One week earlier, the COVID-19 pandemic had begun to grip the nation and widespread lockdowns were taking place. But at 10:30 that night, the couple received a phone call from Mount Sinai’s transplant team that offered tiny Nathaniel a potential lifeline: the family of a shooting victim in his early 20s, who had just died in another state, were willing to donate his liver—epitomizing the “good news/bad news” world of organ transplants.

At the time, operating rooms throughout New York City were being converted into intensive care units to house severely ill patients with COVID-19 who were beginning to strain the city’s health care system, and many hospitals had started suspending their transplant procedures altogether. The hospital where the donor had died told Mount Sinai’s Recanati/Miller Transplantation Institute that its surgeon Chiara Rocha, MD, and her team would have to bring their own personal protective equipment to wear while extracting and retrieving the donated liver to bring back to New York. Charter airline companies were shutting down flights and Mount Sinai’s administrators worked their magic in securing a Learjet to fly Dr. Rocha and her team hundreds of miles to and from the donor hospital in the middle of the night.

“The stars lined up,” says Sander S. Florman, MD, Director of the Recanati/Miller Transplantation Institute. “This was as logistically complicated as anything we have ever done and in a child where everything was stacked against him.”

To this day, Nathaniel’s doctors do not know what caused his rapid liver failure. But now, the inquisitive 20-month-old toddler “is going to do great,” says Dr. Florman. Three-quarters of the liver he received was transplanted into an adult patient at Mount Sinai, who is also doing well.

Members of Mount Sinai’s Liver Transplant team include, from left: Antonios Arvelakis, MD, Associate Professor of Surgery; Marcelo E. Facciuto, MD; Sander S. Florman, MD; and Chiara Rocha, MD.

The liver is the only organ in the body that can regenerate and grow. “But what most people don’t know is that if the liver is too big for the body it can shrink down,” says Dr. Florman. This is significant because at the time of his transplant surgery Nathaniel weighed only 11 pounds, representing “the extreme technical complexity” of what was possible, he adds.

Most children requiring a transplant would receive 20 percent of an adult liver—a size much too large for Nathaniel. Before the transplant could take place, Marcelo E. Facciuto, MD, Professor of Surgery at the Icahn School of Medicine at Mount Sinai, had to cut the donor liver down to the “smallest anatomic segment” possible, says Dr. Florman. But even that was too big. Following the seven-hour surgery led by Dr. Florman, the team left Nathaniel’s abdomen open for four days in order to shrink the liver to a size that was able to fit inside his tiny body.

After conducting more than 4,500 transplants during its 32-year history, Mount Sinai’s program has encountered a challenging surgery like Nathaniel’s only a dozen or so times, says Dr. Florman. “You’re talking about sewing an artery that’s just a couple of millimeters with sutures that are as fine as your hair. You are connecting the artery, the veins, and the bile duct, and it is all done with what we call a loop—glasses with a built-in microscope lens because it’s too small to complete with just your eyes.”

He adds, “Transplant is the epitome of a team sport and you can’t do this without having a tremendous team or without an institution that has unbelievable depth. Only a small number of transplant centers in the country would have been willing to take on a child this small. Even in the best of times this would have been a great triumph and a great case. This was even more so considering the time in which it happened.”

In fact, March 2020 marked the busiest month ever for Mount Sinai’s liver transplant program, which conducted 23 transplants, some of which were referrals from other programs that had just shut their doors.

Image of health 20-month-old Nathaniel among his toys

Today, at 20-months of age, Nathaniel is on track to hit all of his milestones. He is walking on his own, beginning to talk, and able to eat tiny pieces of solid food.

Nathaniel recently celebrated the one-year anniversary of his life-saving surgery, and his prognosis is good. Each month that goes by lowers the chances that his body will reject his transplanted liver. He has been weaned off of all but one of his 13 medications.

“Dr. Florman and his team were just amazing,” says Nathaniel’s father, Dennis Capelo. He and Nathaniel’s mother, Alexandra Ramos, remained at the hospital with their child during the five-month ordeal. Nothing could have prepared them for “the scariest time we ever had to deal with,” says Mr. Capelo, who has a 3-year-old son and 10-year-old daughter from a prior relationship.

He says, “We try to cherish every moment we have. We spend as much time as possible with all of the kids and each other and hope for the best.” He and Ms. Ramos have remained close to Nathaniel’s former Mount Sinai nurses and send them photos and videos to mark their toddler’s milestones, including his first steps. “They became like family to us,” Mr. Capelo says.

One of Nathaniel’s physicians, Ronen Arnon, MD, Professor of Pediatrics, Hepatology, and Liver Transplantation at the Icahn School of Medicine at Mount Sinai, remembers how “Nathaniel struggled to survive. The first months of his life were spent in a hospital bed rather than at home, and his first friends were his doctors and nurses. He suffered from eating and breathing difficulties and he could barely move due to his swollen abdomen.”

Another of his physicians was John Bucuvalas, MD, Chief of Pediatric Hepatology, Professor of Pediatrics, and Director of Solid Organ Transplant Outreach, Jack and Lucy Clark Department of Pediatrics, and Mount Sinai Kravis Children’s Hospital. “Today, Nathaniel is an active toddler and exploring his world. He won’t remember the transplant,” Dr. Bucuvalas says. “But for his parents, the Intensive Care Unit, P5 (Pediatric floor 5) teams, and the liver team, the series of events are etched in our memory and remind us of why we do what we do.”

A Vaccine Pod Dedicated to Mental Health Patients

From left: Raymond Rene, Office of Mental Health (OMH); Ruth Llanos, OMH Psychiatric Nurse; Paul Michael Avellaneda, OMH Psychiatric Nurse; Michelle Izmirly, DO; Gariy Livshits, OMH Treatment Team Leader

Earlier this year, the New York State Office of Mental Health (OMH) launched a program to bring vaccine doses to mental health patients, as many have trouble navigating the internet or don’t have smartphones and need help facilitating appointments. The OMH program was designed for patients to come to state psychiatric centers, but they were also eager to expand their reach and offered to set up vaccine pods at all OMH licensed clinics across the state. Michelle Izmirly, DO, Medical Director of Ambulatory Psychiatry at The Mount Sinai Hospital, reached out to OMH so that The Mount Sinai Hospital’s clinic could be included as a site.

“We see a very vulnerable patient population, and I knew a lot of our patients weren’t comfortable going to places like the Javits Center,” said Dr. Izmirly. “Some were even crying because they were so scared and so frustrated; often, they lacked internet access or cellular service to navigate the New York State vaccine eligibility website. We’re the ones they know. They know our setting and our staff, and they’re more comfortable getting the vaccine with us. They were so grateful that they had this option.”

It was a true team effort to pull it off. OMH scheduled a site visit to make sure the clinic had the appropriate setup: strong Wi-Fi, a comfortable area for injections, and supportive staff. Rajvee Vora, MD, Vice Chair of Clinical Affairs for the Department of Psychiatry, collaborated with Ania Wajnberg, MD, Medical Director of Ambulatory Care at The Mount Sinai Hospital and Site Lead for Vaccine Operations. They engaged the pharmacy and engineering departments to ensure the clinic had the appropriate equipment to safely store the vaccine.

Due to special efforts by Patricia Lamb, Chief of Ancillary and Support Services, Sue Mashni, PharmD, Chief Pharmacy Officer, and Michael Roche, PE, Senior Director of Engineering, the clinic space was converted to a safe and effective vaccine pod in one week. Eva Bayon, Administrative Manager, and Joan Bell, LCSW, Clinical Director of Ambulatory Psychiatry Services, handled the logistics of confirming and scheduling patients. Alicia Hurtado, MD, Associate Dean for Medical Student Wellness and Student Affairs, arranged for medical students to volunteer to monitor the patients for 15 minutes after they received the vaccination.

On April 8, the team vaccinated 72 patients—10 every 30 minutes starting at 9:30 am. And this might only be the beginning. The vaccine pod was such a success that OMH will return May 6 to reach the patients who were unable to attend their appointment that day. If OMH continues to provide the doses, the clinic could continue to offer it to their patients moving forward.

Cassidy Leverett, a care coordinator at the clinic, believes that the stability for these patients is key. “A lot of people find it really difficult to schedule the vaccine because it can be far from where they live or work, so it’s really great that people can go to a place they’re familiar with and see faces that they know. It’s been a very crazy time so it’s nice to have one stable place where you can go get your vaccine.”

Dr. Izmirly hopes this spreads beyond her clinic to other mental health clinics and practices. “You see so many news stories and research studies about people with mental illness contracting and dying from COVID-19 at higher rates than those who don’t suffer from mental illness,” she said. “We’ve even lost some of our own patients, which was completely devastating. This is an opportunity to help our own patients in our own settings, where we know they’ll feel comfortable.”

 

Enduring Racial Slurs and an Assault, Medical Student Oranicha Jumreornvong Speaks Out Against Asian Hate

Oranicha Jumreornvong, center, took to the microphone at an Anti-Asian Hate rally in March.

The rise in Asian hate crimes—including an assault she experienced herself—has transformed third-year medical student Oranicha Jumreornvong into an outspoken advocate for the rights of Asians in the United States.

In March, Ms. Jumreornvong helped organize an anti-hate rally in New York City on behalf of White Coats Against Asian American and Pacific Islanders Hate. The rally drew an estimated 1,000 supporters, including Senator Charles Schumer, D-NY; New York City mayoral candidate Andrew Yang; and 100 health care workers, including 50 classmates from the Icahn School of Medicine at Mount Sinai. 

“Speaking out is not really an option in Thailand, where I’m from,” says Ms. Jumreornvong, 26, who grew up under military dictatorships and widespread censorship. She arrived in the United States in 2014 as an undergraduate at Stanford University. All of her family members live in Thailand. “Thai people learn to minimize things to try to get along,” she adds. “In the past, I would advocate through research but not by public speaking because it conflicts with my own upbringing of trying not to stir up problems.”

“I think the first step to healing is to recognize there is a problem, and I implore everyone to stop viewing the Asian American Pacific Islander community as a model community of wealthy and educated people and, instead, as a heterogeneous group.” — Oranicha Jumreornvong

But her reluctance to speak out against hate ended abruptly on a chilly morning in February, on the Icahn Mount Sinai campus, at 97th Street and Madison Avenue. That is when a stranger wearing a mask yelled “Chinese virus” at her before following her, kicking her, and dragging her across the pavement, as bystanders looked on. The attacker grabbed Ms. Jumreornvong’s cell phone and ran off. The police have not yet found him.

“I was on my way to get my first COVID-19 vaccine at Mount Sinai before returning to work at the hospital later that day,” says Ms. Jumreornvong. “I had a coat on over my scrubs. I told him, ‘I’m a medical student,’ and at first he seemed okay with that and I thought he would leave me alone. But then he didn’t.” After the attack, Ms. Jumreornvong’s mentors in the Department of Rehabilitation Medicine and Human Performance checked on her via telemedicine and a friend who is a resident in Physical Medicine and Rehabilitation tended to her wounds

Ms. Jumreornvong had been the victim of a bias incident several months earlier, while she was in between shifts at Mount Sinai Morningside. She was alone on a bench eating a granola bar when a woman pushing a child in a stroller told her to put her mask on and go back to China.

Support from friends and mentors outside and within the Mount Sinai community has helped ease her pain. “Mount Sinai has always been supportive emotionally and in terms of advocacy work,” she says. After her assault, Mount Sinai’s medical students started a petition to denounce anti-Asian hate and the Health System quickly embraced it. “I feel like Mount Sinai has provided me with this privilege—this platform to speak out—and that I have to do something, and by helping others I’m also healing.”

Oranicha Jumreornvong, front row, fourth from the left, and her colleagues from White Coats Against Asian American and Pacific Islanders Hate, drew an estimated 1,000 supporters to their rally in Manhattan’s Chinatown neighborhood.

In raising awareness about anti-Asian hate, Ms. Jumreornvong wants the public to view the Asian community as a diverse group of people. There is a lot of poverty among Asian groups, she says, and many are underrepresented in medicine and other professions.

“I think the first step to healing is to recognize there is a problem, and I implore everyone to stop viewing the Asian American Pacific Islander community as a model community of wealthy and educated people and, instead, as a heterogeneous group,” she says. She would like to see the establishment of scholarships that help underrepresented Asian groups and the elimination of health disparities that exist in poor Asian American communities. She would also like the U.S. medical community to recognize some of its own unconscious biases.

After her painful experiences in the United States, Ms. Jumreornvong’s father in Thailand was concerned for her safety. She assured him that she would be all right.

“As an immigrant, I have an American dream too,” she says. “America is so diverse and you see people of different colors and ethnicities come together. I consider this my second home, so I don’t want to leave it. You can choose to weigh yourself down with bitterness. I think it’s easier on the soul to heal through kindness and resilience.”