Curing Cancer With 
Living Drugs

Bianconi immediately started a standard regimen of treatment, first chemotherapy and then radiation, at Dartmouth Cancer Center. She stayed upbeat during the months-long process, getting out to ski in the afternoons following treatment sessions, and seeing both her daughter and son get married.  

Despite her optimism, the standard treatments failed. She was given six months to live.  

But Bianconi was offered one final option: a relatively new immunotherapy treatment called chimeric antigen receptor (CAR) T-cell therapy.  

“At that point, CAR T-cell therapy was considered the last resort,” says Bianconi, who was the 13th patient at Dartmouth Cancer Center to receive CAR T-cell therapy. “When you know this is your last chance, you begin to prepare for war. You are fighting for your life.” 

 While many standard treatments, such as chemotherapy and radiation, blast cancer cells with toxic chemicals to kill them, CAR T-cell therapy takes a different approach. As a type of immunotherapy, it coaxes a patient’s own immune system into fighting cancer.  

A newcomer to the field of cancer treatments, CAR T-cell therapy is just beginning to prove its potential, in part thanks to Dartmouth’s own trailblazing researchers.  

“Cell therapy is transforming how we treat cancer. These drugs have long-lasting benefits and let people go back to being people and not just cancer patients,” says Konstantin Dragnev, MD, interim director of Dartmouth Cancer Center. “At Dartmouth Cancer Center, we are building upon a history of discovery and innovation to lead that charge.”  

Dartmouth discoveries have been laying the groundwork for immunotherapy since the 1970s, and today new investments in Dartmouth Cancer Center’s research and clinical infrastructure are cementing that legacy, as the Cancer Center launches a center for cell therapy to bridge critical gaps between cutting-edge research and life-saving clinical care. With an influx of new initiatives, Dartmouth researchers are making incredible progress to develop CAR T-cell therapies and other cell therapies, for curing not only cancer but a range of other diseases as well.  

Rebooting the Body

Cell therapies—a category of immunotherapies—work by supplementing an immune system’s own cells. Every day, cells in our bodies mutate into potentially cancerous cells. Normally, the body’s immune system quickly identifies and destroys these irregular cells. But in some cases, the cancer cells can evade the immune system. Those irregular cells multiply and eventually grow to a level that causes noticeable symptoms, as with Bianconi’s stomachaches.  

With CAR T-cell therapy, doctors harvest a patient’s T cells—white blood cells that are the immune system’s frontline soldiers, responsible for destroying irregular cells—and modify them with a synthetic receptor, known as a chimeric antigen receptor, or CAR. When the cells are placed back in the body, the new receptor allows the cells to recognize, attack, and destroy cancer cells they couldn’t previously detect.  

A great benefit of CAR T-cell therapy is that it effectively creates a living drug within the patient. “With chemotherapy, you have to kill every last cancer cell, otherwise you don’t get long-term survival because those cells will grow back,” says Marc Ernstoff, MD, director of experimental cell therapy at Dartmouth Health. But “the immune system has memory, and has the ability to keep an eye on things over time.”  

T cells, for example, survive for a long time in the body and can continue to recognize and attack irregular cells that develop long after the initial cancerous cells are dealt with. This means it only needs to be administered once to remain operational in the patient over a long time, possibly even permanently curing the patient of that type of cancer.  

“It’s just something that we never imagined possible,” says Mary Jo Turk, PhD, O. Ross McIntyre Endowed Professor and co-director of the Immunology and Cancer Immunotherapy Program at Dartmouth Cancer Center, whose research laboratory focuses on generating durable memory T-cell responses to cancer.  

The idea behind cancer immunotherapy has been around for over a century. In fact, the concept of harnessing the body’s immune system to treat cancer was first tested when William B. Coley injected cancer patients with bacteria at a New York hospital in the late 1800s. Though Coley’s tests had promising results, his methods didn’t catch on. It would take decades for immunotherapy to be widely accepted as a cancer treatment.  

Dartmouth has always been at the forefront of cancer immunotherapy. When Dartmouth Cancer Center was founded in 1972, immunotherapy was one of its initial programs. Shortly thereafter, in 1977, one of the main proteins that causes T cells to grow and fight cancer, interleukin-2, was discovered at Dartmouth Medical School by Kendall A. Smith, MD, and then-PhD student Steven Gillis.  

A decade later, in 1987, Dartmouth Medical School immunologists Michael Fanger, PhD, Paul Guyre, PhD, and Edward Ball, MD, founded Medarex, a biopharmaceutical company that would develop antibody drugs for patients. Medarex was the first to bring to patients a drug that used antibodies to block an inhibitor of T-cell function, freeing up T cells to kill cancer cells.  

The potential of immunotherapies to treat cancer really started to grow in the early 2000s as the next generation of Dartmouth researchers took to the labs. It was around that time that Charles Sentman, PhD, a professor of microbiology and immunology at the Geisel School of Medicine at Dartmouth and director of the Center for Synthetic Immunity, started studying CAR T-cell therapy at Dartmouth. Back then, he says, the number of researchers worldwide investigating CAR T-cell therapy could fit in a small conference room. Researching a kind of immune cell called natural killer cells, Sentman helped lay the groundwork for several first-generation CAR T-cell therapies. This work helped propel Dartmouth as one of the early leaders in cell therapy.  

The next few years saw a slew of successes with CAR T-cell therapy and other immunotherapy treatments. The work that started at Medarex led to immunotherapy drugs called ipilimumab and nivolumab, which showed impressive clinical efficacy in fighting melanoma and were approved by the FDA in 2011 and 2014. In 2013, Science magazine called cancer immunotherapy the “Breakthrough of the Year,” and in 2018 the Nobel Prize in Physiology or Medicine was awarded to a Medarex collaborator for advances in treating cancer with T-cell-based immunotherapies.  

Today, that small room of researchers has ballooned to hundreds, including dozens of pharmaceutical companies. In 2020, Dartmouth began providing the first FDA-approved CAR T-cell therapy treatments to its patients, and in 2025 it offered a new experimental CAR T-cell treatment in clinical trials. Today, several research teams at Dartmouth are developing half a dozen different types of cell therapy drugs in pre-clinical trials.  

The Missing Piece

Although its history is filled with success in cell therapy, Dartmouth Cancer Center has been missing one key capability ever since the first experiments were run in the 2000s: the ability to manufacture novel experimental therapy products to be used in clinical trials for patients. Nationwide, there are only a handful of specialized facilities certified to do this. This means that Dartmouth discoveries have long faced challenges overcoming what those working on drug development call a “valley of death,” says Ernstoff. New drugs can hold lots of promise in the laboratory, he explains, but translating them into a clinical setting poses new challenges that require special infrastructure, techniques, and skills: in this case, producing cells that can actually go into patients in clinical trials.  

“At Dartmouth, we are poised on one side with good laboratory science, and we’re poised on the other side with outstanding clinicians that know how to do clinical research, but we need to build a bridge between the two,” Ernstoff says. 

With a foundational grant and the support of ongoing fundraising efforts, this will soon come to fruition, as Dartmouth Cancer Center launches its new center for cell therapy, named IMPACT: Integrated Multidisciplinary Program for Advanced Cell and Gene Therapies. With Ernstoff at the helm, the philanthropy-powered center will give patients access to cutting-edge experimental cell therapies as soon as they’re available. Housed in new dedicated spaces slated to open this year at Dartmouth Health’s Dartmouth Hitchcock Medical Center, the new center will be able to manufacture Dartmouth’s own CAR T cells, as well as similar treatments like nanoparticle and small-molecule drugs and protein therapeutics. This, Ernstoff says, will “allow us to be a member of a relatively elite group of centers that are able to translate their science quickly into the clinic.”  

Having a dedicated facility will give Dartmouth researchers the ability to conduct clinical trials entirely in-house, which will give Dartmouth Health patients more options as soon as they’re available and enable Dartmouth researchers to more quickly test the next generation of cell therapies.  

“Making a living drug isn’t easy—everybody’s cells are different and there are logistical challenges with having to ship off cells to a manufacturing facility,” Sentman says. “If we can do all that here now, that’ll be a huge benefit for our cancer patients.”  

Life After Cancer

For Bianconi, who participated in an industry-conducted clinical trial, her T cells had to be shipped to a manufacturing facility in California before she could begin treatment at Dartmouth Cancer Center. Two months later, the modified cells were put back in Bianconi’s body on August 29, 2022. One day went by, then two, with no side effects. But on the third day, Lisa felt like she had been hit by a truck. The drug had started to work.  

“I’m not going to sugarcoat it,” Bianconi says. “It was hard.”  

CAR T-cell therapy helps patients avoid the life-altering side effects of traditional treatments like fatigue, hair loss, nausea, and “chemo brain.” However, CAR T-cell therapy has its own side effects, such as flu-like symptoms and a weakened immune system. Infection due to a weakened immune system is one of the greatest risks with CAR T-cell therapy, and so patients are closely monitored in the hospital for three weeks following treatment, when they are most at risk.  

For Bianconi, things had improved by the second week. Shortly after, she transitioned to outpatient care and then was able to continue recovering at home. By January 2023, two years after her first stomach pains, she was back working full-time at her job as director of music at Kurn Hattin Homes for Children and has been relapse-free ever since. She recently celebrated her 40th year as a teacher, for which she credits CAR T-cell therapy.  

“Who would ever think that doctors could send away your cells, modify them, and put them back in your body to cure cancer? It’s like something from a sci-fi movie,” Bianconi says. “It’s a miracle. And it saved my life.”  

For More Than Cancer

While still in their infancy, cell therapies are showing great success in treating a range of cancers. There are many CAR T-cell therapies that are FDA-approved and working well, and there are hundreds of ongoing clinical trials around the world for new treatments for everything from lung cancer to blood cancer.  

At Dartmouth, researchers have several promising and patented treatments in the pipeline for which they’d like to run clinical trials. These include CAR T-cell therapies for multiple types of cancers and solid tumors, which represent the bulk of cancers but have historically not responded to CAR T-cell therapies.  

“We’re really excited about these treatments,” Turk says. “They all have very promising pre-clinical results in animal testing and growing amounts of data on their efficacy on human cancer cells as well.” But cell therapies aren’t just for cancer—some trials are showing promise against life-threatening autoimmune diseases and immunodeficiencies, such as lupus, Crohn’s disease, and HIV. Sentman’s lab is now working on CAR T-cell therapy applications to neurological diseases like Alzheimer’s, Parkinson’s, and ALS.  

“Cell and gene therapy is a vital tool for the future of cancer treatment,” Sentman says. “But, going forward, it’s also going to be a way of treating complex diseases from autoimmunity to neurological.”