Cancer | Mount Sinai Today

Novel Cancer Immunotherapies Show Promise

Updated on Jun 30, 2022 | Cancer, Featured, Research

A PET-CT scan indicates one patient’s partial response to the in situ vaccination after six months. as shown in pre-vaccine, left, and six months post-vaccine.

Researchers at the Icahn School of Medicine at Mount Sinai are pioneering two novel approaches to cancer immunotherapy that are promising for patients with non-Hodgkin lymphoma and other solid tumors, which have been stubbornly resistant to therapies such as checkpoint blockade.

One new approach is an in situ vaccination that worked so well in patients with advanced-stage lymphoma that it is now undergoing trials for breast cancer, as well as head and neck cancers. The other therapy captures the synergy of checkpoint blockade and stem cell transplantation in the form of a highly promising treatment known as immunotransplant. Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program and Assistant Professor of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai, is the lead investigator for both therapies.

The In Situ Vaccination

This vaccination approach involves injecting immune stimulants directly into a single tumor site, which “teaches” the immune system to recognize and destroy cancer cells at that site and throughout the body. “We’re teaching dendritic cells—the generals of the immune system army—to specifically recognize tumor antigens, which then instruct the T cells, the immune system’s soldiers, to go forth and kill the cancer cells while sparing non-cancer cells,” says Dr. Brody.

As reported in the April 2019 issue of Nature Medicine, this therapy involves several steps that begin with injection of a small molecule that calls the dendritic cells to action, followed by low-dose radiation to kill the tumor cells. These dying cells, in turn, release antigens into the immune system that are recognized by the dendritic cells and presented to the T cells as part of the “coaching” process.

The results were encouraging among a cohort of 11 patients with non-Hodgkin lymphoma. In earlier tests with lab mice, the vaccine was able to cure about 40 percent of lymphoma tumors, Dr. Brody says. When combined with checkpoint blockade, the cure rate nearly doubled. Dr. Brody reports that when testing the therapy in patients, “We saw some who had profound regressions of their entire tumor burden. After treating one site, tumors throughout the body melted away.”

The next step in the development of the vaccine began last spring when Mount Sinai began recruiting patients for a clinical trial that combines the vaccine therapy with checkpoint blockade—a widely used treatment that effectively removes the brakes from T cells so they are free to attack cancer cells. This trial will target lymphomas, as well as breast cancer and head and neck cancers.

Immunotransplant Therapy

While PD-1 blockade has been effective for some lymphoma patients, its ability to help those with non-Hodgkin lymphoma has been more challenging. Even anti-PD-1/anti-CTLA4 dual checkpoint blockade has yielded limited efficacy, perhaps due to insufficient T cell activation.

Recently, Dr. Brody and his team found that combining immunotherapy and stem cell transplantation may be beneficial. In this first-of-its-kind approach, reported in Cancer Discovery, the researchers were able to increase the cancer-killing immune response tenfold when tested in the lab, making it effective against not just non-Hodgkin lymphoma but also melanoma and lung cancer.

“In the lab, immunotransplant either prolonged survival greatly compared to immunotherapy alone or actually cured a significant portion of mice with melanoma and lung cancer,” Dr. Brody says.

Immunotransplant works through the principle of homeostatic proliferation: when T cells are put into an empty organism or body, they become activated and begin to wildly multiply. In immunotransplant, T cells are withdrawn from the blood through apheresis, clearing the way for their reintroduction as infused immune cells. As they proliferate, these reinvigorated T cells build the immune system back up, become activated, and enable checkpoint blockade to achieve its full cancer-fighting potential.

The fact that checkpoint blockade has become the standard of care for treating melanoma, kidney cancer, lung cancer, and other diseases underscores the promise of immunotransplant. “We’ve shown we can increase the power of checkpoint blockade immunotherapy to prolong survival and induce cures in aggressive cancers, and that means not just lymphomas but solid tumor types,” says Dr. Brody.

Gynecologic Cancer Awareness Health Fair

Oct 21, 2019 | Cancer, Community

Rachel You, BSN, RN, left, and Hanna Cho, BSN, RN.

More than 500 participants learned about self-care and cancer risk factors at the Gynecologic Cancer Awareness Health Fair in Guggenheim Pavilion. The event, on Thursday, September 19, was sponsored by Women’s Services at The Mount Sinai Hospital and included nutrition tips, music, spiritual care, yoga, and information about support groups. This year, about 100,000 cases of gynecologic cancer will be diagnosed in the United States, says Godsfavour Guillet, BSN, RN, Nurse Manager, who organized the fair with the Women’s Health team on Klingenstein Pavilion 4.

Stephanie V. Blank, MD, Director of Gynecologic Oncology, Mount Sinai Health System, and Director, Women’s Cancer Program at the Blavatnik Family – Chelsea Medical Center at Mount Sinai, says, “By learning about symptoms, and measures that can reduce risk, you can empower yourself to make health decisions that can literally save your life.”

The nursing team from Klingenstein Pavilion 4 organized the event. Front row, from left, Jennifer Winborne, Assistant Director; Rachel You, BSN, RN; Godsfavour Guillet, BSN, RN, Nurse Manager; Petrina James, BSN, RN; and Hanna Cho, BSN, RN. Back row, from left: Justin Lyttleton, Business Associate; Ali Karim, Patient Care Associate; Diandra Mitchell, Patient Care Associate; Micaela Cruz, BSN; Vereen Gouldburne, BSN; Irena Durkovic, BSN; Monique Bartholomew, Patient Care Associate; and Erin Figueroa, MSN, RN, Senior Director.

Study Links Dust at Ground Zero to Prostate Cancer

Sep 9, 2019 | Featured, Prostate Cancer

Eighteen years after the September 11 attacks, Mount Sinai Health System researchers have found a higher incidence of prostate cancer among the World Trade Center (WTC) first responders than other populations, suggesting that chronic inflammation can facilitate the development of prostate cancer.

Emanuela Taioli, MD, PhD; and William Oh, MD

The most recent findings, published in June in Molecular Cancer Research, were led by Emanuela Taioli, MD, PhD, Director of the Institute for Translational Epidemiology and Associate Director for Population Science at The Tisch Cancer Institute; and William Oh, MD, Chief of the Division of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai, and Deputy Director of The Tisch Cancer Institute.

“Our research supports the first line of evidence that acute World Trade Center dust exposure through inhalation can profoundly disturb gene expression and immune cell infiltration in the prostate,” says Dr. Taioli.

While working at Ground Zero, the first responders did not wear protective gear and were exposed to dust particles composed of volatile organic compounds from jet fuel, as well as asbestos, benzene, silica, glass fibers, polychlorinated biphenyls, polychlorinated dibenzofurans, and dioxins from the collapsed buildings. Given the fine particulate nature of the WTC dust, the researchers hypothesize that the toxins entered the blood through the lungs and eventually reached the prostate and other distal organs.

“The results of this study support our hypothesis that exposure to the dust at the World Trade Center caused chronic changes in the body,” says Dr. Oh. “The long-lasting inflammatory effect in the prostate revealed in our study calls for further investigation as to the effect of this exposure in other organs, such as the kidney or thyroid, or the central nervous system.”

In 2018, Dr. Taioli led a study published in the European Journal of Cancer Prevention, which reported that responders who spent more time working at Ground Zero and had a higher exposure to the dust cloud that formed after the WTC buildings collapsed, had more advanced stages of prostate cancer—stages III and IV—representing tumor invasion. Interestingly, the 2018 study found that at the beginning of their service at the WTC, the responders were mostly nonsmokers of diverse ethnic backgrounds who were considerably healthier than the general population and at lower risk for cancer.

According to the recent 2019 report, approximately 20 percent of human cancers are thought to be caused by chronic infection or inflammatory states, and chronically unresolved inflammation is related to increased risk of malignant disease. When tested in the laboratory, the toxic dust was shown to induce the secretion of cytokines— small proteins involved in modulating responses to inflammation infection, cancer, and trauma.

Mount Sinai runs the largest World Trade Center Health Program Clinical Center of Excellence in the New York metropolitan region, with 25,000 patients who have consented to participate in research. A biobank of more than 600 cancer samples from first responders has helped lay the groundwork for Mount Sinai’s WTC research findings.

Dr. Taioli says the latest research raises additional questions about whether air pollution, in general, causes an inflammatory response in people. “This work has larger implications for the population exposed to environmental particulates, such as emissions from motor vehicles, industrial processes, power generation, and the household combustion of solid fuel,” she says. “Inflammation could be the common pathway driving an increase in cancer occurrence.”

Push-Up Challenge Brings Awareness to Prostate Health

Updated on Jun 30, 2022 | Community, Prostate Cancer

More than 120 Mount Sinai Health System faculty and staff completed more than 6,000 push-ups at the recent fourth annual Push-Up for Prostate Cancer Challenge held in Guggenheim Pavilion. The event, which commemorated Prostate Cancer Awareness Month in September, challenged each individual to complete 29 pushups in honor of the 29,000 men who die from prostate cancer in the United States each year.

“This very important event reflects Mount Sinai’s commitment to prostate cancer,” said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System, who kicked off the challenge by completing 96 push-ups.

Dr. Tewari, left, and Dr. Charney, far right, with winner John Mendez.

Dr. Tewari, left, and Dr. Charney, far right, with winner Daphne Semet, MBA.

Dr. Tewari, left, and Dr. Charney, far right, with The Mount Sinai Hospital Urology team.

The first-place team trophy was awarded to the Department of Urology at The Mount Sinai Hospital, which completed 775 push-ups. Individual awards were given to the top male and female, as well as to the individual who completed the most modified push-ups. First place honors were given to John Mendez, Customer Service Representative, Department of Plastic and Reconstructive Surgery (male, 101 pushups); Daphne Semet, MBA, Vice Chair of Administration and Finance, Department of Pathology, Molecular and Cell-Based Medicine (female, 102 push-ups); and Mena Singh, MPA, Senior Accountant, Department of Finance (modified-style, 106 push-ups).

Push-Up Challenge Brings Awareness to Prostate Health The program also offered information about prostate cancer and provided cancer screenings and risk consultations. “Prostate cancer is one of the most common cancers, but it does not produce any symptoms, and the only way you can go after it is by being proactive,” said Ash Tewari, MBBS, MCh, the Kyung Hyun Kim, MD Chair in Urology, Mount Sinai Health System, who led the event.

National Cancer Institute Leader Visits Mount Sinai

Nov 5, 2018 | Cancer, Community, Featured, Research

From left: Luis M. Isola, MD, Professor of Medicine (Hematology and Medical Oncology), and Pediatrics; Ramon Parsons, MD, PhD, Director, The Tisch Cancer Institute; Norman E. Sharpless, MD, Director, National Cancer Institute; and William Oh, MD, Deputy Director, The Tisch Cancer Institute, and Associate Director of Clinical & Translational Research for the Institute.

Aging is one of the greatest risk factors for developing cancer, which is most frequently diagnosed among people aged 65-74. But there are no simple explanations for the “multifaceted” science behind this connection, according to Norman E. Sharpless, MD, Director of the National Cancer Institute (NCI).

On Thursday, September 13, Dr. Sharpless addressed the topic in a seminar titled “The Dynamic Interplay between Cancer and Aging,” which he presented before a standing-room-only crowd in Davis Auditorium on The Mount Sinai Hospital campus. Dr. Sharpless has devoted much of his career to studying the connection between cancer and aging. Developing a better understanding of this relationship is particularly important, he said, because people over the age of 65 make up the fastest growing segment of the nation’s population.

Dr. Sharpless was invited to speak about his own research by The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, where he spent the earlier part of the day meeting with leaders of the Institute and medical school. He had lunch with postdoctoral fellows and students who work in Mount Sinai’s cancer-focused laboratories, and met with faculty and staff who oversee Mount Sinai’s Cancer Center Support Grant. The grant provides Mount Sinai with its NCI designation as one of an elite group of U.S. institutions committed to the research and treatment of cancer.

During the day’s meetings, Dr. Sharpless shared his vision for NCI programs and discussed trends in funding and cancer research. The Tisch Cancer Institute received its NCI designation for the fi rst time in 2015 and is preparing to renew the competitive grant in 2019. Since his appointment to the NCI in 2017, Dr. Sharpless has spent time visiting NCI-designated cancer centers around the country. On his recent trip to New York City, he also visited the Albert Einstein Cancer Center.

Do I Need a Biopsy or Surgery for My Thyroid Nodule?

Updated on Jun 30, 2022 | Head and Neck, Your Health

Thyroid nodules are very common. These masses within the thyroid gland are composed of tissue and/or fluid and are estimated to be present in more than 50 percent of those aged 50 and older. Nodules can run in families, are more common in women, and increase in frequency with age.

Patients diagnosed with a thyroid nodule often ask if their nodule needs to be biopsied or surgically removed. Sometimes the answer is yes, but often the answer depends on a number of patient and nodule-related factors. Catherine Sinclair, MD, FRACS, head and neck surgeon at Mount Sinai West, explains why your nodule may, or may not, need special attention.

How do you know if you need a biopsy?

More than 95 percent of thyroid nodules are non-cancerous, although a family history of thyroid cancer in a first-degree relative or whole-body/neck/chest radiation exposure may increase the risk. Nodules have a low cancer risk, so whether to biopsy depends on the size and ultrasound appearance of the mass.

Over the past decade, many nodules smaller than one centimeter have been incidentally detected on imaging (CT, MRI) that was ordered for another reason. Often these nodules were inappropriately biopsied, and, if the biopsy was positive for thyroid cancer, overly extensive total thyroid surgery was performed. Recent data from Japan and the United States suggests that appropriately selected thyroid cancers can remain stable over time. Termed “microcarcinomas,” these cancers are less than one centimeter in size and may be adequately managed without surgery or with limited thyroid surgery.

How is risk measured?

In an effort to reduce “incidentally diagnosed” microcarcinomas, the American Thyroid Association (ATA) Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer classifies nodules into risk categories for biopsy based on thyroid nodule size and ultrasound appearance. Those classified as high-risk nodules should be biopsied when more than one centimeter in size, whereas low-risk nodules—depending on their appearance on ultrasound—should not be biopsied until they are one and a half to two centimeters in size. Many thyroid surgeons perform their own ultrasounds and use the ATA risk classification system (along with any biopsy results) to determine who should have a biopsy, which nodules should be operated on, and which nodules can be safely observed.

What are the symptoms and treatment for thyroid nodules?

In addition to posing a cancer risk, nodules may also need to be removed if they grow very large (greater than four centimeters) and cause symptoms like difficulty swallowing, neck discomfort, hoarseness of the voice, and airway compression with shortness of breath. Frequently, a thyroid lobectomy—the removal of a portion of the thyroid gland—may be adequate treatment for a non-cancerous thyroid nodule as well as for small cancerous nodules that are less than four centimeters. However, patients should speak with their surgeon in detail beforehand about the many additional factors affecting surgery, such as the status of the other thyroid lobe, your age, and your personal preferences.

In summary, a thyroid nodule may require an operation if there is a high risk of the nodule being cancerous or if the non-cancerous nodule is large and causing symptoms.

Non-cancerous nodules that are asymptomatic should be observed with intermittent ultrasound follow-up when appropriate. If surgery is necessary, the least aggressive option that will effectively treat the nodule should be chosen.