What is Cellular Therapy?
Cellular therapy has proven to be a successful treatment for many diseases and conditions, and holds enormous promise for even more patients and indications. Cellular therapy by definition is the administration of cells with the intent of providing therapeutic effector cells in the treatment of disease or support of other therapy. These effector cells potentially function in different ways: to produce mature blood cells that carry oxygen, fight infection, help blood to clot, or serve an immunological function; to grow or differentiate into muscle or cartilage tissue; or to repair damaged tissues. The cellular therapy field is exploding! Distinguishing established or promising cellular therapies from those that are theoretical at best and misleading at worst may be challenging. Yet, the potential of cells to cure diseases or improve quality of life is real and provides reason for optimism.
History of Cellular Therapy
Cellular therapy’s origins date to 1957, with E. Donnall Thomas’s initial report of intravenous infusion of bone marrow cells following radiation and chemotherapy, a radical new approach to the treatment of cancer. Malignant cells, or normal cells destroyed by chemotherapy or radiation therapy, could be replaced by normal, blood forming cells from a donor. Although only a few of these first recipients showed evidence of engrafted cells, continued research into improved donor selection, supportive care, and management of complications led to cures in a few, otherwise incurable, leukemia patients during the early 1970s, and subsequently, to marked improvement in survival among cancer patients treated earlier in the course of their disease. Some bone marrow derived progenitor cells, called hematopoietic stem and progenitor cells (HPC), also have an immune function that plays an important role in eradicating cancer. These and other discoveries in cell transplantation in the treatment of human disease led to the awarding of the 1990 Nobel Prize to Dr. Thomas, shared with Joseph Murray who performed the first successful kidney transplantation.
HPCs also function to replace defective or deficient cells, as seen in patients with severe combined immunodeficiency (SCID), an inherited disease characterized by overwhelming infections and often, early death in infancy. In 1968, Dr. Robert A. Good and his team successfully transplanted bone marrow cells from a sibling to repopulate the immune system of an infant with SCID, opening the way for treatment of many other congenital and acquired human disorders, including aplastic anemia and hemoglobin disorders such as thalassemia and sickle cell anemia. HPCs are also used for their ability to produce normal enzymes in some serious cases of inherited enzyme deficiency.
Sources and Types of Cells
HPCs are found in the bone marrow space, and can be collected directly from the bone marrow, usually from the hip bones, during a surgical procedure. A very small percentage of progenitor cells normally circulate in the peripheral blood. Using medications or growth factors, it is possible to increase the percentage of circulating progenitors, allowing collection of HPCs from peripheral blood using apheresis techniques. Umbilical cord blood is also rich in HPCs and has become an important source of cells, especially for pediatric patients and patients with rare tissue types.
Donors of hematopoietic progenitor cells can be allogeneic or autologous. Allogeneic cells are normal cells donated by one person for administration to another person. Initially, allogeneic donors were identical twins or closely matched siblings. Following the 1979 publication of the first successful HPC transplant from a matched unrelated donor to a child with leukemia, efforts intensified to establish a registry of healthy, tissue-typed persons willing to donate cells for an unrelated patient in need. For information on how to sign up for the National Marrow Donor Program as a potential donor, visit www.bethematch.org.
Autologous donors are patients whose HPCs can be collected, processed, and stored prior to treatment, and infused to restore hematopoietic function after high dose therapy. This is only possible when normal cells can be obtained without contaminating cancer cells.
In addition to HPCs, other therapeutic cell populations can be obtained, and then processed, treated, or manipulated in the laboratory with the intent to administer them to patients for prevention or treatment of a disease or injury. Such cells can proliferate, differentiate, respond, and act by multiple mechanisms to achieve a therapeutic effect to repair, replace, or regenerate missing or damaged tissues. Examples include:
- Immune cells, such as activated T-cells, B lymphocytes, and monocytes
- Cancer cell vaccines and dendritic cells
- Mesenchymal stem cells, such as adult stem cells present in marrow, cord blood, and other tissues that may differentiate into a variety of cell types potentially useful in regenerative medicine
- Mature cellular preparations derived from solid organs, such as islets and hepatocytes
These cell products are in various stages of research and development, and may be available only in clinical trials. Research is underway on many other sources of cells, including skin, teeth, menstrual blood, and amniotic fluid; however, these sources are in early stages of research and their value has not yet been proven.
Balancing Hope and Realism in Cellular Therapy
Cellular therapy is an exciting field with seemingly infinite possibilities. Enthusiasm for cellular therapy is encouraging to both the researchers who hope to use it to save more lives and to the public searching for the newest promised cure, often desperate after standard therapy has failed. It is important to be able to distinguish legitimate clinical trials and innovative therapies from unregulated practices that may pose unacceptable risk, delay more effective therapy, or make patients ineligible for clinical trials. Useful indicators of legitimate cell therapies include voluntary accreditation by professional organizations, noteworthy scientific publications and reputation of the providers, and the information available related to potential risks and benefits of the proposed therapy prior to full, voluntary informed consent.
The Foundation for the Accreditation of Cellular Therapy (FACT) accredits cellular therapy programs and cord blood banks based upon demonstrated compliance with standards that have been developed by international experts in the field. Standards encompass the entire cellular therapy process, from donor selection, product collection, processing, storage, and administration. Accreditation requires submission of written documents and a rigorous on-site inspection conducted by volunteer international experts. Organizations that achieve FACT accreditation have developed and implemented a foundation of quality practices resulting in cell products and patient care highly sought by physicians and patients. Most programs accredited to date are HPC transplant programs and/or cord blood banks; however, accreditation of facilities processing other types of cells is increasing. To find accredited programs, visit the FACT website at www.factwebsite.org.
Basic and translational research and clinical trials are critical to the success of cellular therapy, and participation in clinical trials is encouraged. Such participation will provide you and/or your loved ones with access to cutting edge care while also assisting researchers in their quest for lifesaving cures. To find clinical trials in cellular therapy and other fields, visit www.clinicaltrials.gov.
