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Cellular therapies are designed to improve the immune system's ability to fight cancer. Manufacturing them involves collecting a specific set of cells from the blood, modifying them to produce a more vigorous attack on a patient's cancer cells, and then reinjecting them into the patient.
Cellular therapies differ from stem cell transplantation in that the cells collected are not blood-forming stem cells. Instead, they may be certain types of immune system cells, including a subgroup of T cells capable of killing tumor cells. They may also be tumor cells themselves that have been re-engineered to draw an attack by the immune system. And, unlike the cells used in a classical bone marrow transplant, the collected cells are altered before being infused back into the patient.
The Cellular Therapies Program at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) builds on our expertise in stem cell transplantation. Cells are processed at an outside commercial facility or at the Connell and O'Reilly Families Cell Manipulation Core Facility, which has long been at the forefront of producing cell-based therapies for cancer and other diseases.
Many types of cellular therapy for cancer are being explored, including CAR T cells, other genetically modified T cells, and vaccines.
Chimeric antigen receptor, or CAR T-cell therapy, is a new form of cell therapy that uses specially altered T cells to more specifically target cancer cells. Currently, it is available only in clinical trials.
The immune system is made up of specific cells and organs that protect the body from infection and cancer. Among these are T cells, which hunt down and destroy abnormal cells, including cancer cells.
After a sample of a patient's T cells has been collected from the blood, the cells are re-engineered so they sprout special structures called chimeric antigen receptors (CARs) on their surface. When these CAR T cells are reinjected into the patient, the receptors may help the T cells identify and attack cancer cells throughout the body.
T cells are collected by a process called apheresis. From a needle in the patient's arm, blood flows through a tube and into an apheresis machine, which separates out the T cells and returns the rest of the blood cells to the other arm. The procedure is done in one day in a clinic at the Kraft Family Blood Donor Center at Dana-Farber Cancer Institute and Brigham and Women's Hospital.
The collected cells are genetically engineered, at Dana-Farber or a special lab, to produce the CAR protein. They are then prepared for infusion back into the patient. The process of engineering the cells and producing sufficient quantities of them can take a few weeks. In the meantime, patients may receive chemotherapy for their cancer.
When the CAR T cells are ready, patients are admitted either to Dana-Farber's Inpatient Hospital located within Brigham and Women's Hospital (BWH) or to BWH, where the cells are infused in a process similar to a blood transfusion, usually preceded by several days of preparative chemotherapy. During this time, patients may get medications to prevent and control possible side effects of the newly-engineered cells. At this time, patients need to stay in the hospital for a few days or even several weeks, depending on their condition and the risk of side effects.
Throughout the entire process, careful measures are in place to ensure patients' safety.
As a new approach to cancer treatment, CAR T-cell therapy is being tested in clinical trials for a wide variety of tumor types. Although these trials are ongoing and the results are very preliminary, the best results to date have been obtained in blood cancers such as lymphoma and leukemia.
At DF/BWCC, clinical trials of CAR T-cell therapy are now underway for several different types of cancer. Trials are also in progress involving other types of T cell therapies. Speak with your care team for more information about cellular therapy clinical trials.
Cancer vaccines represent another approach to marshaling the immune system's disease-fighting forces against cancer. Some of these vaccines consist of cancer cells, parts of cells, or immune-stimulating proteins called antigens. Others involve removing some of a patient's white blood cells and exposing them to a protein from the cancer, along with a stimulatory molecule. The process primes the white cells to attack cancer when they're reinjected into the body.
One type of cell-based vaccine involves removing certain immune system cells from a patient's blood and sending them to a lab. There, they are exposed to chemicals that turn them into dendritic cells, which display cancer-related antigens on their surface. The dendritic cells are combined with a stimulatory protein that prompts a robust immune response on tumor cells. The newly energized dendritic cells are infused back into the patient through a vein. The process may be repeated several times, a few weeks apart, so patients receive multiple doses of the cells. The side effects are usually mild and can include fever, chills, fatigue, back and joint pain, nausea, and headache. Provenge®, a prostate cancer therapy that is the only vaccine approved to treat cancer in the U.S., is an example of a dendritic cell vaccine. This approach is under investigation in other cancers as well.
Another approach is to construct a vaccine out of cancer cells that have been removed from the patient during surgery. The killed tumor cells are processed in a lab to make them more "visible" to the immune system, then re-injected into the patient along with an immune-stimulating compound. The patient's immune system launches a vigorous attack not only on the newly-injected cancer cells but also on similar cells throughout the body.
Protein-based vaccines represent still another way to "teach" the immune system to confront cancer cells in the body. This approach is based on increasing immune system's ability to detect tumor antigens, proteins on the surface of tumor cells that advertise the cells' cancerous identity. Patients first undergo surgery to have the bulk of their tumor removed. Cells from the tumor are sent to a lab where they are engineered to display new antigens indicative of cancer. Reinjected into the patient, the cells are primed to draw a strong, focused immune system attack on other cancer cells in the body.
At DF/BWCC, investigators are leading clinical trials of this type of vaccine, known as NeoVax, in patients with melanoma or glioblastoma brain cancer.
Cellular therapies are being expanded for the treatment of many different types of cancer and non-cancerous diseases. Patients should check with their care team about the availability of such therapies for their particular condition.
At Dana-Farber/Brigham and Women's Cancer Center, clinical trials of cellular therapies are now underway for the treatment of an expanding number of cancer types and non-cancerous diseases. We encourage you to check with your care team for more information about the availability of cellular therapy trials for your particular condition.