The Duke Cancer Institute Center for Cancer Immunotherapy connects physicians, scientists, and researchers to discover immunotherapies for every cancer type. Immunotherapies boost the immune system's ability to kill cancer. The Center’s mission is to develop and test new immunotherapies, new indications for immunotherapies, and new combinations of drugs that include immunotherapies. They hope to accelerate the journey from animal and cell studies to human clinical trials, and drug manufacturing, when possible.
CAR T-Cell Therapy
Chimeric antigen receptor (CAR) T-cell therapy is one example of an immunotherapy that is offering new hope to some lymphoma patients. CAR T-cell therapy involves removing white blood cells called T cells from a patient’s body, genetically modifying the cells in a lab, and then infusing them back into the patient. Unlike a pharmaceutical with a defined chemical formulation, each batch is made from living cells of an individual patient.
This therapy is approved for people who have failed at least two lines of treatment for several kinds of non-Hodgkin’s lymphoma: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Duke Cancer Institute was one of the earliest treatment centers certified to administer CAR T-Cell therapy when it was approved by the FDA in October of 2017.
Many Studies Underway
CAR-T therapies for some solid tumors are in clinical trials. The Preston Robert Tisch Brain Tumor Center is studying a CAR-T therapy for glioblastomas, a type of brain cancer.
Duke investigators also have several studies under development to learn how to use immunotherapies to target cancer and to the ramp up the immune system to fight cancer.
The Duke Cancer Institute Center for Cancer Immunotherapy is interested in potential opportunities for collaboration from the bench to the bedside across the entire spectrum of cancer types. We are actively looking for the development of strategic research partnerships to generate scientific synergy. Whether there is interest in translating a concept into a different scientific field or building research teams for future grant proposals, the Duke Center for Cancer Immunotherapy is interested in helping investigators through the process.
The Duke Cancer Institute Center for Cancer Immunotherapy is the nexus for physician-scientists and researchers across DCI who are focused on developing new immunotherapies as well as testing, in clinical trials, new immunotherapies, new combinations of drugs that include immunotherapies, and current immunotherapies for new indications. The center is comprised of known thought leaders in their respective fields who look for cancer immunotherapy discoveries that show promise, no matter the cancer type.
The DCI Center for Cancer Immunotherapy aims to speed up the process that brings immunotherapies for cancer from the bench to the bedside. We’ve been able to accomplish in six months what might take years at another institution by drawing on the collaborative talent of Duke investigators. Our investigators are engaged in every step of the process, from conducting lab studies to designing clinical trials and manufacturing a drug. We are open to collaborating with research partners across the world to broaden the scope of cancer patients who may benefit from immunotherapy treatment.
More research efforts are under development at our center, including new lung cancer immunotherapies and immunotherapies that will fight head and neck cancer, upper gastrointestinal cancer, colorectal cancer with metastasis to the liver, melanoma, and bladder cancer.
The Hanks Lab, run by Brent Hanks, MD, PhD, immunotherapy resistance. Understanding why some patients respond to immunotherapy and others don’t may guide the development of novel strategies to overcome resistance and expand the number of patients who can respond to immunotherapy.
Ongoing research in the Hanks Lab focuses on understanding how malignancies develop their own strategies for evading anti-tumor immunity and becoming resistant to currently available immuno-therapeutics. The lab utilizes both genetically engineered tumor models as well as clinical specimens from patients undergoing immunotherapy to guide their research. The group is currently conducting studies in melanoma, non-small cell lung cancer, and colorectal cancer.
This area of investigation holds great promise for using immunotherapies to treat people with cancer.
Brent Hanks, MD, Ph.D, Andrew Nixon, Ph.D., and Jennifer Choe, MD, Ph.D., are collaborating on a biobank to understand why some patients develop autoimmune responses that inflame the gastrointestinal tract, lungs, and liver, or lead to the destruction of endocrine glands, including the thyroid and pituitary. The biobank collects blood and tissue samples, and data on reactions, from Duke cancer patients treated with immunotherapy for various cancer types. Data from this project will help predict which patients are at risk for side effects so they can be proactively managed or even prevented.
Disease-Specific Research Projects
Several projects are underway to study immunotherapies in breast cancer, gastrointestinal cancers, genitourinary cancers, lung cancer, and melanoma.
Novel Therapeutics Development
The Hanks Lab is working to develop drugs that target and manipulate dendritic cells to boost immune responses to checkpoint inhibitor therapy.
Georgia Beasley, MD, a surgical oncologist, is conducting clinical trials evaluating intra-lesional therapeutics such as oncolytic viral vectors to help manage patients with advanced melanoma. She is conducting clinical studies evaluating these agents that have been developed by other biotech companies.
April K.S. Salama, MD, leads ongoing clinical efforts to improve the management of patients with melanoma that has spread to the brain.
An investigational therapy for solid tumors could be especially effective when combined with immunotherapy to target a specific kind of cancer cell, a research team at Duke and Harvard has found.
Led by Lee Zou, PhD, chair of Duke’s Department of Pharmacology & Cancer Biology, the researchers focused on the way some cancer cells impede normal DNA repair to fuel tumor formation. This phenomenon is known as defective DNA mismatch repair.
DCI member Jose Ramon Conejo-Garcia, MD, PhD, (left), worked with co-authors Mostafa Eysha, PhD; Luis Bailon, PhD; and co-senior author Carmen Anadon, PhD, on an antibody approach for precision cancer treatment. (Photo by Les Todd)
For too long, cancer treatment has been a double-edged sword – the very treatments designed to kill cancer cells often wrought havoc on healthy ones too.
But a new study published online Oct. 30 in Immunity, a Cell Press journal, unveils an approach to cancer treatment that researchers describe as more precise, long-lasting, and less toxic than current therapies.
The work, led by Duke University School of Medicine immunologist Jose Ramon Conejo-Garcia, MD, PhD, centers on the innovative use of IGA antibodies to target and kill tumor-promoting molecules, found deep within cancer cells, that have long eluded existing treatment options, including IGA antibody treatment.
Afreen Shariff, MD, assistant professor in the division of Endocrinology, Metabolism and Nutrition, has been selected by the Association of Community Cancer Centers (ACCC) as a 2023 Innovator Award recipient for her work on the effectiveness of electronic consults for immune-related endocrine toxicities.
Shariff in 2020 created the acuity-based Duke Endo-Oncology Electronic Consultative Service, which has since done consults for more than 300 patients. The biggest gain has been the cost-saving impact as Shariff reduced both the time to appointment and hospitalizations from 61 days to 39 days and from 11% to 2%, respectively. (See New Endo-Oncology Program is Reducing Wait Times and Hospital Admissions.)
“We have been able to provide value-based, high-impact service that saves lives, patients time and it turns out we also save the system hundreds of thousands of dollars with admissions we have been able to prevent,” said Shariff, an endocrinologist with expertise in endocrine disease in cancer patients. “This has been a win-win situation for everyone, oncologists, us and most importantly our patients, who deserve to continue effective cancer treatments while worrying less about how side effects will be managed.”
part of a Special Report by Duke Cancer Institute & the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report (pdf)
Oncologists today have a wider range of anti-cancer drugs to reach for, many of which target the molecular alterations believed to contribute to the cancer’s development.
Comprehensive genomic profiling, also known as next-generation sequencing (NGS), is used to identify these molecular alterations. Duke Cancer Institute (DCI) oncologists partner with Duke University Health System (DUHS) Clinical Labs and private diagnostics companies to test patients at diagnosis and/or after the cancer grows or spreads.
While it can vary across cancer types, increasingly, targeted therapies that can save patients from needing toxic chemotherapy are becoming available at multiple points in a patient’s cancer treatment, from first line standard of care to subsequent treatment after progression on conventional therapies.
Test results are entered into a Molecular Registry of Tumors known as Frameshift MRT. This centralized informatics tool — designed, built, and coded at Duke byMichael Datto, MD, PhD, (currently the medical director of DUHS Clinical Labs and vice chair for Clinical Pathology) and Christopher Hubbard (DUHS clinical informatics architect) — helps oncologists identify if anything in their patient’s mutational profile, even extremely rare targets, can be treated with any existing targeted therapies or immunotherapies.
Duke Cancer Institute has been offering its patients NGS testing since 2014. Developing Frameshift MRT three years later to organize and optimize the growing volume and complexity of data, and the subsequent formation, in early 2018, of a weekly multidisciplinary Molecular Tumor Board to review complex patient cases was a perfectly timed great leap forward.
The Precision Cancer Medicine Initiative — launched in 2017 by DCI, the BioRepository & Precision Pathology Center (BRPC), and the Clinical Labs — was the critical push behind it.
“It had become increasingly clear that the needs of sophisticated cancer researchers were changing across all cancer types; moving away from generic, archived, cancer-tissue samples, to fresh samples, to samples with a specific molecular abnormality,” explains Shannon McCall, MD, director of the BRPC, a DCI and Duke University School of Medicine Shared Resource housed in the Department of Pathology. “This coincided with clinical advances. Providers, including at DCI, were utilizing these broad molecular profiling assays to direct the care of cancer patients. There was a need to harness all this molecular profiling data to support both cancer research and treatment. I was totally on fire to get this started. We have so many big thinkers at Duke who said, ‘Let’s think about data and what’s possible.’”
In mid-2018, Executive Director of DCI Michael Kastan, MD, PhD, a noted cancer biologist, and Chair of the Department of Pathology Jiaoti Huang, MD, PhD, a prostate cancer researcher, signed a memorandum of understanding to co-fund the staffing necessary to further support the Molecular Tumor Board — co-directed by oncologists John Strickler, MD (for solid tumor cancers), and Matthew McKinney, MD (for blood cancers) — and to manage the Frameshift MRT database. This included hiring a bioinformatician/ data analyst (Jonathan Bell, PhD) and a savvy genetics scientist (Michelle Green, PhD).
Green, fresh from a position in the molecular diagnostic testing industry, joined the Duke Pathology (with salary support from DCI) in the spring of 2019 as senior research program leader of the Molecular Tumor Board and main user and manager of Frameshift MRT. She tracks promising clinical trials and new FDA drug approvals and has configured Frameshift MRT to automatically send therapy alerts to providers when their patients' molecular profiles match any known anti-cancer drug(s). This match could include drugs that are already FDA-approved, drugs that are “emerging” with strong clinical evidence, drugs that are being tested in clinical trials, or drugs that are approved or being trialed in another cancer type.
Over the course of the COVID-19 pandemic, Green has made several significant changes to Frameshift MRT that make it more user-friendly, interactive, and accessible for clinicians and researchers, who can access the Frameshift MRT dashboard when logged into the Duke VPN. Green is available to train and advise.
When Joseph O. Moore, MD, came to Duke as a fellow in 1975, he and his mentors treated chronic myeloid leukemia (CML) with a chemotherapy regimen that was like a “wet blanket.” It suppressed the cancer for a few years. “But it didn’t change the trajectory of the disease,” Moore said. Patients developed acute leukemia, which was almost always fatal.
By the early 1990s, younger patients could achieve a cure with a bone marrow transplant, though complications were common. By 1999, Moore was the Duke investigator for a national study of a targeted drug, imatinib, which stops leukemia cells from growing by shutting down a key protein.
When imatinib was approved by the Food and Drug Administration (FDA) in 2001, it transformed CML into a disease easily treated by taking a pill.
When Moore retired from clinical practice in 2019, he was involved in a study following people with CML who had been taking imatinib long term, which showed they could safely stop therapy.
The CML example provides a snapshot of just how far cancer treatment has come in the last 50 years. For many patients, “There’s an expectation of success and people living normal lives,” said Moore, professor emeritus of medicine.
Much of that progress can be traced to research funded by the “war on cancer,” which launched in 1971 when congress passed the National Cancer Act. The act gave the National Cancer Institute (NCI) the authority and funds to create a national cancer program. The backbone is a network of comprehensive cancer centers that provide patient care and conduct rigorous research to find new and better ways to prevent, diagnose, and treat cancer.
Lung Cancer survivor Henrietta Carr presents a cancer ribbon-themed wall hanging to physician assistant Susan Blackwell, October 2021. (photo by Les Todd)
On October 12, just before her 66th birthday, Henrietta Carr surprised her care team with a cancer ribbon-themed wall hanging she’d embroidered.
“When I was diagnosed with stage 4 lung cancer, I moved from Greensboro to Durham so I could get treatment at Duke; I just wanted to come to Duke because I think they’re better,” says Carr. “I was feeling hopeless and as I was being treated by Dr. Crawford and Susan Blackwell, I started feeling hopeful of a future. They would share in my happiness, as the cancer would shrink. I am so grateful to my cancer team and wanted to show this gratitude.”
Carr, a mother of two adult children, began embroidering cancer-ribbon-themed wall hangings to support individuals with cancer — friends, friends of friends, family, and friends of family — after she retired from nearly 30 years of service as a clerk and IT specialist for the Social Security Administration. This was well before she was diagnosed with cancer.
“I did about 30 individual pieces and sent them out across the United States,” says Carr, who continued to embroider after her cancer diagnosis. It took about 25 hours to create the 36 by 56 (inches) piece she made for her cancer care team.
To be diagnosed with cancer after bringing so much joy to other individuals with cancer was an unfair turn of events, Carr agrees. “But it is, what it is,” she says.
It’s been nearly two years since Carr’s diagnosis. She’d gone to the Emergency Department at a hospital in Greensboro feeling a little fatigued and hoarse and came out of the ED with a diagnosis of pneumonia, which she was subsequently treated for. However, within a few weeks, she’d lost her voice and was hurting in her chest. Her second trip to the same ED resulted in a diagnosis, by an oncologist there, of lung cancer and pneumonia.
“It was in both lungs and in between my lungs,” says Carr, noting that she wasn’t coughing or experiencing any breathing problems at the time. “I was kind of surprised. Because they kept saying it was (only) pneumonia.”
Not Too Late
In April 2020, she began radiation treatments to her right lung under the care of DCI radiation oncologist Christopher Kelsey, MD. She would also receive various combinations of chemotherapy and immunotherapy. There were promising clinical trial results at the time that indicated that chemotherapy and immunotherapy taken in combination might be more effective than either alone, Crawford explained.
In December 2020, she underwent radiation to her left lung. Since then, she has been on immunotherapy (Keytruda, pembrolizumab) alone.
Carr's specific diagnosis was lung adenocarcinoma, the most common primary lung cancer in America. This particular type of non-small cell lung cancer (NSCLC) has a strong association with previous smoking.
Carr smoked cigarettes. As soon as she learned she had lung cancer, she tried to quit. With the aid of DCI physician assistant and trained tobacco cessation specialist Kelly M. Young, PA-C, she “cut way back.”
“Quitting smoking can be extremely difficult and at times patients may not even know where to start,” said Young. “I value being able to help patient accomplish their goal of quitting smoking by offering medications and counseling based on the most current research.”
People who currently smoke or have ever smoked make up more than 80% of lung cancer diagnoses. Quitting smoking can reduce your chance of developing lung cancer. Even after developing cancer, Young explained, quitting smoking can make cancer treatment more effective and prevent recurrence of cancer or new cancers from developing.
By the end of this year, more than 235,000 new cases of lung cancer will have been diagnosed in the U.S. While the number of annual lung cancer deaths is decreasing, it remains the leading cause of cancer death in the U.S. (not including skin cancer). Lung cancer will take the lives of roughly 132,000 people in the U.S. this year — including about 5,000 in North Carolina — estimates the American Cancer Society.
A Path to Home
More than 75% of lung cancers are diagnosed in people over the age of 65. Carr, 66, has been on treatment for more than a year and a half and is still going strong.
She’s even cheery. She says she feels “much, much, better,” though she admits she doesn’t have a lot of energy.
In September 2021, Carr and her sister Sharlene were able to settle into a new house back in their hometown where they have extended family — in an area down towards Wilmington, not far from the Duplin Winery.
Her treatments have now been extended to once every 6 weeks. She drives an hour-and-a-half to her immunotherapy infusion appointments and clinic visits at Duke Cancer Center in Durham, her sister by her side, and at the end of the day they drive right back home.
“It’s going good. I feel pretty good,” said Carr, who describes herself as a homebody who avoids crowds. “We are just enjoying our house. And staying away from the Delta COVID.”
Susan Blackwell, MHS, PA-C, and Jeffrey Crawford, MD, have been caring for patients with lung cancer at the Duke Cancer clinic for more than 30 years and are more excited than ever about the many treatment options now available.
They work especially closely with primary clinical nurse, Mallory Tassone, BSN, RN, thoracic oncology fellow, Hilary Dietz, MD (who's training in medical oncology), and radiation oncologist Christopher Kelsey, MD, in a team approach for the benefit of their patients.
Susan noted, “Ms. Carr is a wonderful person, always thinking of the needs of others. She is a true lung cancer survivor, living well and living longer.”
The link between estrogens and breast cancer has long been defined, but a Duke-led research team has identified how these hormones can also influence the growth of other cancers, notably melanoma.
Building on observations that male melanoma patients who are treated with immune checkpoint inhibitors tend to have better responses than women, the team found that estrogens are a likely driver of the differences in outcomes.
The researchers reported their findings in a study appearing Oct. 12 in the Journal of Clinical Investigation.
Read the press release.
Postdoctoral fellow Binita Chakraborty, PhD, was intrigued: in published analyses of large numbers of patients with melanoma (skin cancer) treated with an immunotherapy that is becoming standard of care, the treatment worked better in men than in women.
“There may be multiple reasons why the response may be different between males and females,” she says. “But one of the biggest differences that stands out was circulating estrogen levels. Estrogen levels are much higher in females than males.”
As a breast cancer researcher, Chakraborty knows a bit about estrogen. When she told her mentor, Donald McDonnell, PhD, that she wanted to explore what was really behind this connection, he told her to run with it.
Her findings are leading to a Duke clinical trial in the works that may make immunotherapy work better for people with melanoma, as well as other cancers.
New to studying skin cancer, Chakraborty knew just who to call—Duke physician-scientist Brent Hanks, MD, PhD, who treats patients with melanoma and studies the disease. Hanks helped her establish tumor cell lines and mouse models that mimic humans with melanoma. The mice have mutations that are present in up to 70 percent of people with the disease—a mutation in a protein called BRAF and a deletion in a different protein known as PTEN.
In all the tests that Chakraborty did with these mice, estrogen increased cancer growth. But not in experiments with isolated tumor cells in culture dishes.
“When we cultured the tumor cells, then put in estrogen, they were not growing faster or doing anything,” Chakraborty says. “None of these tumor cells themselves were actually responding to estrogen.”
That told her that the estrogen must be influencing something in the tumor “microenvironment” – the community of cells that surrounds the tumor and nurtures its growth. “The tumor tries to hijack the environment around it to help itself grow faster,” Chakraborty says.
To find out how estrogen is making melanoma worse, she did experiments in a mouse that doesn’t have a functional immune system. In those mice, whether she treated with estrogen or not, the tumor growth stayed about the same. “That got us to hypothesize, okay, estrogen must be affecting the immune cells in the microenvironment,” she says. “The tumor is growing fast in response to estrogen only when the immune cells are present.”
The tumor microenvironment contains many different types of immune cells, but Chakraborty found that in melanoma, estrogen particularly affects one type—macrophages. She explains that normally there is a balance between “good” macrophages, which can help alert T cells to a tumor so they can kill it, and “bad” macrophages, which help a tumor grow by promoting blood vessel growth and impairing T cell function.
In mice with melanoma, estrogen shifts the balance toward the bad macrophages.
Chakraborty shared these findings with Scott Antonia, MD, director of the Duke Cancer Institute for Cancer Immunotherapy, to get his perspective as a clinician. He was immediately interested. Unbeknownst to Chakraborty, Antonia had been studying lung cancer patients who had stopped responding to an immunotherapy called a PD-1 inhibitor. In these patients, “bad” macrophages were increased in proportion to “good” macrophages. Just like in Chakraborty’s mice with melanoma.
So, Chakraborty did some experiments in mouse models of non-small-cell lung cancer. She found that estrogen increased “bad” macrophages in lung cancer too.
Based on these results, Antonia is now writing a clinical trial to combine a newer anti-estrogen drug used to treat breast cancer with a PD-1 inhibitor, in patients with melanoma, non-small cell lung cancer, and gastric (stomach) cancer. He hopes that inhibiting estrogen will improve patient responses to this type of immunotherapy.
“Binita is firing on all cylinders,” McDonnell says. Even while she and her husband, a scientist at UNC-Chapel Hill, juggle homeschooling their six-year-old son during the COVID-19 pandemic, she is having many of the early successes that can prepare her for becoming a faculty member. And McDonnell is thrilled. “I still get a buzz out of publishing papers, but I get a much bigger buzz out of seeing the next generation of cancer researchers succeed and get on their way,” he says.
DISCLOSURES: Donald McDonnell, PhD, is involved in the company developing the drug that will be used in the clinical trials mentioned in this story.
This article appeared in the Winter 2021 issue of Breakthroughs magazine. Breakthroughs is produced twice yearly by Duke Cancer Institute Office of Development.
William Blake, 65, worked for the State of West Virginia for about 35 years in the toll division before taking early retirement in 2007 when he got sick with follicular lymphoma. He was treated at Charleston Area Medical Center (WV) and survived that cancer.
But when Blake was diagnosed four years later with a different type of cancer at the Beckley, WV, Veterans Hospital — metastatic melanoma to the brain — he was referred to Duke.
John Kirkpatrick, MD, PhD, the director of radiation oncology for The Duke Center for Brain and Spine Metastasis at Duke Cancer Institute and clinical director of radiation oncology at DCI, performed an image-guided stereotactic radiosurgery (SRS) procedure on Blake’s two brain lesions — a high-tech non-surgical therapy that delivers precisely-targeted high-dose radiation in one to five treatments, while preserving nearby healthy tissue.
Medical oncologist April Salama, MD, meanwhile, treated Blake with a course of ipilimumab, an immunotherapy that had just been approved that year for the treatment of advanced melanoma. When another lesion appeared in March 2012, Kirkpatrick “disappeared” that one as well.
“The prognosis was “We’ll do what we can, the mets are really small, and we caught it early,”” said Blake, who’s today making the most of his retirement.
While Blake has recently had some small localized melanomas and basal cell carcinomas removed in other areas of his body, there’s been no sign of cancer in his brain for seven years.
On January 31, 2018, Duke Cancer Institute joined a select group of medical centers across the country (34 to date) certified and trained to administer Yescarta, the first Food and Drug Administration-approved CAR T-cell therapy for the treatment of adult patients with certain types of relapsed or refractory non-Hodgkin’s lymphoma. Duke Cancer Institute is currently the only center in the region — South Carolina, North Carolina, and Virginia — offering this immunotherapy.
Chimeric antigen receptor T-cell therapy, better known as CAR T-cell therapy, is unlike any other cancer treatment. The individualized gene therapy transforms a patient’s own T-cells (white blood cells) into CAR T-cells designed to recognize, attack, and destroy cancerous B cells.
“With CAR T-cells, using the patient's own immune system to fight cancer has become a reality,” said Director of DCI’s Hematologic Malignancies & Cellular Therapy Program, Nelson Chao, MD, MBA. “The early data has been very encouraging and exciting.”
Manufactured by Kite Pharma, a Gilead company, Yescarta is the brand name for axi-cel (the short name for axicabtagene ciloleucel), which is FDA-approved to treat patients who have not responded to treatment or who have relapsed after receiving two or more other forms of systemic treatment for the following types of non-Hodgkin lymphomas (large B-cell lymphomas):
Diffuse Large B-cell Lymphoma (DLBCL) not otherwise specified
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
High-Grade B-cell Lymphoma
DLBCL arising from Follicular Lymphoma (FL)
It is not indicated for the treatment of patients with Primary Central Nervous System (CNS) Lymphoma.
Eligibility & Treatment
Patient eligibility for Yescarta therapy depends on several factors. Based on a comprehensive evaluation, patients may be offered a consultation with a doctor who specializes in this therapy or offered other lymphoma treatment options that are better suited to their health situation, including active surveillance, radiation therapy, targeted therapy, chemotherapy, and/or stem cell or bone marrow transplant. The Hematologic Malignancies and Cellular Therapy program also offers a variety of clinical trials for the treatment of lymphomas including other investigational CAR T-cell therapies.
If patients are appropriate for Yescarta therapy, approval is sought from their medical insurance provider.Once approved, they will visit the Adult Blood & Marrow Transplant (ABMT) Clinic, located at Duke’s North Pavilion, where they will undergo apheresis, a relatively painless four-hour outpatient procedure in which white blood cells (T cells) are removed from the bloodstream to be used to manufacture Yescarta. The collected cells are immediately walked down the hall to the Stem Cell Lab where the cells are frozen, packaged, and then shipped out the same day to Kite’s state-of-the-art commercial manufacturing facility in El Segundo, CA. There the cells will be re-engineered, frozen again, and shipped right back to Duke — about a 17-day process.
Five days before the patient is to be infused with their “new” cells at Duke University Hospital (Inpatient Unit 9100), they undergo three consecutive days of lymphodepleting chemotherapy at the ABMT Clinic, followed by a day of rest. Then the patient is admitted to the hospital. The following day, they receive their autologous infusion and stay in the hospital for about seven days for active surveillance. Following this, they are monitored daily, as an outpatient, at the ABMT Clinic for the next four weeks. (Patients must commit to staying within a half-hour radius during this time. They are given contact information for local apartment options as well as rooms at the DCI-affiliated “home away from home” Caring House.)
Chao warns that the highly specialized and highly personalized therapy is not without its serious risks — high fever, serious flu-like symptoms, sudden drops in blood pressure, and seizures, but points out that “it’s an exciting step forward in providing a potentially curative option for patients that have failed other forms of treatment.”
So far there are a handful of patients under evaluation at Duke for the Yescarta therapy.
At Duke, A CAR T Future
As a National Cancer Institute-designated Comprehensive Cancer Center, DCI’s Hematologic Malignancies & Cellular Therapy specialists treat 1,000 people with blood cancer each year, more than any other facility in North Carolina. It was this high level of expertise coupled with Duke’s pre-existing infrastructure, that enabled Duke to be certified to offer Yescarta following FDA approval.
“Duke has had a long history of focusing on immune-based therapies, developing various cancer vaccines, remaining on the cutting edge of allogenic transplant immune therapy, and now involvement in multiple monoclonal antibody and engineered T-cell immuno-based therapies,” said Hematologic Malignancies section chief David Rizzieri, MD. “Harnessing the power of one’s own immune system to attack cancer has been a goal for decades. It allows us to turn from standard chemotherapy to targeted immune stimulation using the body’s own normal defense mechanisms. This is just the first step of many in the next few years that will allow us to take an entirely new direction in cancer therapy to improve outcomes.”
Duke Cancer Institute’s Hematologic Malignancies and Cellular Therapy program is actively building other CAR T-cell clinical trials, for the treatment of various other hematologic malignancies in adults. At present, there will be no staffing up required to deploy this therapy, but that could change in the future. Hematologic malignancies and cellular therapy specialist Ahmed Galal, MD, FRACP, MSc is the clinical lead for CAR T-cell therapy.
“CAR T-cell therapy has the potential to revolutionize cancer care,” said administrative director of the Hematologic Malignancies & Cellular Therapy Program, Gabriel Alcantara. “This is only the first adult commercial CAR T-cell therapy at Duke. While it’s starting out, for adults, in certain types of non-Hodgkin’s lymphomas, there will be more CAR T therapies in the next few years for other blood cancers, and further down the road, to solid tumor types.”
Duke is also already in the process of becoming certified to administer tisagenlecleucel (brand name: Kymriah, manufactured by Novartis) — the first CAR T-cell therapy FDA-approvedfor the treatment of patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who didn’t respond to treatment or relapsed at least twice — and was one of the sites that participated in the clinical trial that led to its approval.
Patients who are interested in being evaluated for adult CAR-T cell therapy must have their physician provide a referral.