Cell Therapy Adds a New Option to Cancer Treatment
Cell therapy is often said to be a new, "fifth pillar" of cancer treatment — joining surgery, radiation therapy, chemotherapy, and targeted therapy in the cancer armamentarium — but it actually represents a more fundamental change. For the past hundred-plus
years, human intervention, in the form of surgery, radiation, or drugs, has been the driving force of cancer treatment: the physician introduces an outside agent or action that directly targets cancer cells. It is humanity vs. cancer, with no intermediary.
In cell therapy, the immune system takes the lead, with science and technology providing an assist. The immune system brings millennia of experience in fighting cancer; the new therapies supplement that with human ingenuity.
CAR T-cell therapy scored its initial success in patients with blood cancers. In clinical trials, it generated early remissions in more than 80% of patients with B-cell ALL and nearly half of patients with B-cell non-Hodgkin lymphoma, all of whom had
stopped responding to other forms of treatment.
Results like that captured the attention of the scientific world and set in motion a worldwide effort to explore the capabilities of this new therapy, applying it to other kinds of cancer, asking whether it can be made even more effective, and working
on versions that could be pre-made rather than manufactured individually for each patient. The field today vibrates with the energy and creativity more commonly associated with a new art form, as researchers in academia and industry probe its possibilities
and test its potential.
The current roster of clinical trials of CAR T-cell therapies at Dana-Farber for patients with lymphoma illustrate this range. Trials differ by the type of lymphoma being treated and the therapy being tested (different CAR T-cell therapies may target
different proteins on cancer cells). Some trials involve CAR T-cell therapies alone, some involve combination with other therapies. Some target rare types of lymphoma, others deal with more common forms. Some are for adults, others are for children
and young adults.
"As a research institution, we have a lot of optimism about where this field is headed," says Caron Jacobson, MD, MMSc, medical director of Dana-Farber's Immune Effector Cell (IEC) Therapy program, which supports clinical trials of IEC therapies at the
Institute. "Clinical trials of CAR T-cell and other IEC therapies have the potential to benefit patients who have run out of other treatment options. If we can offer trials to patients in that position, we both benefit patients and further the field
as a whole."
As the number of IEC therapy trials at Dana-Farber has grown, so has the size of the staff that supports them. "A standard clinical trial might require a visit to the clinic for blood work once every three weeks. A patient in an IEC trial, by contrast,
might be in the hospital for two to three weeks, with continuous monitoring of vital signs, symptoms, and other information," Jacobson explains. "These steps require an extremely high level of coordination, quality control, and documentation."
CAR T-cell therapies have so far proven far more effective in hematologic cancers such as lymphoma, leukemia, and multiple myeloma than in solid tumors. There are a variety of reasons for this. Solid tumors don't want uninvited guests: their toxic, immune-suppressing
interiors discourage T cells from entering or staying very long. And whereas B-cell lymphoma and ALL cells all carry a single protein marker that can be targeted by CAR T cells, solid tumor cells carry multiple different markers. Nevertheless, researchers
have recently developed new varieties of CAR T cells specifically for solid tumors. Several of these therapies are now in clinical trials at Dana-Farber for lung, breast, cervical, head and neck, gastrointestinal, and other solid tumors.
Each of these trials benefits from the experience Dana-Farber physician-scientists gained in using CAR T-cell therapies to treat patients with hematologic malignancies. The IEC program led by Jacobson ensures that that expertise is shared.
"Each solid tumor disease center at the Institute now has a representative on the IEC program," Jacobson says. "They propose trials that they're interested in opening, and we offer personnel to support them, including clinical research coordinators and
research nurses. We also have physicians trained in cell therapy who can work with solid tumor physicians in managing the patients on these trials."
And because Dana-Farber is home to basic scientists as well as clinical trial leaders, these trials do far more than test whether a new cell therapy is safe and effective. "We're able to learn something from virtually every patient, because we're able
to collect blood, bone marrow, and tumor samples from them and study the samples at a genetic level and an immunological level to understand how these therapies work, why they sometimes don't work, and how they might be improved," Jacobson remarks.