It’s been about half a century since the first transplant of bone marrow from a donor to a recipient was completed. Since then, bone marrow transplantation has become an integral part of care for many patients with persistent leukemia, lymphoma, multiple myeloma and other blood cancers, as well as noncancerous blood disorders such as sickle cell disease. Specifically, we are transplanting stem cells — nascent cells with the capacity to mature into functioning blood and immune system cells — from a matched or partially matched donor into the body of a patient whose own blood-forming system has been destroyed with toxic medication to make way for a healthy new system to grow and develop.

In recent years, however, our field has expanded to include other treatments that work in similar ways as bone marrow transplantation. They are collectively known as “cellular therapies” because they do one of three things: provide healthy new cells to replace diseased cells, release an influx of specially modified immune cells to teach the body’s immune cells how to fight disease, or provide cells that connect immune cells with cancer cells they are designed to kill. Study after study has demonstrated how these approaches are extending patients’ lives. This progression of therapies is reflected in bone marrow transplant services around the country, many of which — including our own at Hackensack University Medical Center — now include the words “cellular therapy” in their names.

It is an exciting time for those of us in the stem cell transplantation and cellular therapy field. For years, we have concentrated on improving the outcomes of stem cell transplants. We have significantly improved techniques to reduce the risk of graft-versus-host disease, a potentially serious complication of transplantation that occurs when immune cells from the donor identify the tissues of the recipient as foreign and attack them, causing a host of inflammatory symptoms. We have learned which medications to give to prevent post-transplant infections such as cytomegalovirus, a common virus that can be damaging in people with compromised immune systems. We are using stem cells from umbilical cord blood to perform more transplants in adult patients. And we have matched more patients with donors by learning how to perform “haploidentical” transplants, where the patient receives a transplant from someone who is partially matched immunologically. These advances are making stem cell transplantation a safer and more effective treatment option for more patients who need them.

But where we are really seeing a revolution in care is the field of cellular therapy — particularly CAR T-cell immunotherapy. Cancer cells have found ways to escape being detected and destroyed by immune cells. Immunotherapies work by helping the immune system find and kill cancer cells.

With CAR T-cell therapy, immune cells called T cells are removed from the patient, genetically modified in a lab to recognize and attach to certain targets on cancer cells, grown to larger quantities (hundreds of millions), and returned to the patient. There, the modified T cells can find, bind to and kill cancer cells. The treatment is given intravenously. Long after the patient goes home, however, his or her newly educated immune cells continue to detect and destroy cancer cells, which is why this treatment is often referred to as a “living therapy.”

CAR T-cell therapies are typically administered in bone marrow transplantation units, and for good reason: Patients receive chemotherapy beforehand, which reduces the immune response. The treatment itself can cause immunologic side effects which, albeit temporary, can be severe — including high fever, body aches and chills. The administration of CAR T-cell therapies requires round-the-clock care from a specially trained and credentialed team. As bone marrow transplant specialists, our experience and knowledge of immunology enable us to recognize and manage the inflammatory complications that may result.

Current CAR T-cell therapies are FDA-approved for the treatment of recurrent or persistent diffuse B-cell lymphoma, follicular lymphoma, multiple myeloma and mantle cell lymphoma (which is a very aggressive and challenging cancer) in adults, as well as acute lymphoblastic leukemia in children and young adults up to age 25. We are intrigued by other innovative cellular therapies under study in clinical trials, such as natural killer (NK) cells and tumor-infiltrating lymphocytes (TILs). These treatments are made from a patient’s own tumor tissue, so it has already been exposed to the patient’s own immune system. Immune cells within a tumor, which on their own were unable to kill the cancer, are isolated from tumor tissue removed during surgery, modified and multiplied in a lab, and returned to the patient with other medications to boost the immune response against cancer.

Not only is the technology getting better, but the types of tumors we are treating is broadening. New CAR T-cell therapies, NK and TIL treatments, and another approach that combines CAR T-cell and NK therapies may broaden the application of these “living therapies” to patients with solid tumors, including melanoma, breast cancer and pancreatic cancer. We’re also looking at combining cellular immunotherapies with stem cell transplantation to augment the anticancer immune response even further.

Cellular therapies are truly game-changers in cancer care. It has been inspirational for us as bone marrow transplant professionals to be part of their development. What we’re witnessing now is just the tip of the iceberg. We’re only getting better at identifying the best immune cells and engineering them in the best fashion to harness the immune system in the most effective way. Discovery is exponential and the field of immunotherapy is growing at warp speed. It’s not impossible to think that we’re going to be curing cancer.

Michele Donato, MD, is chief of the Adult Stem Cell Transplantation and Cellular Therapy Program at John Theurer Cancer Center, Hackensack University Medical Center. 

For the entire article, please click on the link below:

https://www.scientificamerican.com/custom-media/cell-therapies-hit-their-stride/?utm_source=facebook&utm_medium=social&utm_campaign=sacm_hmh&utm_content=link-post&fbclid=IwAR3-Yc7b2DjNxNX62WZPmyVbLxzta8TjrJQsCfGAQwySnt5kNZ4OivQU9KA

 

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