Cell based immune-therapies are proven to be effective for cancers where the immune cells such as lymphocytes, macrophages, dendritic cells, natural killer cells (NK Cell) or cytotoxic T lymphocytes (CTL) work together to defend the body against cancers and attacks by “foreign” or “non-self” invaders such as bacteria and viruses.
Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors. In the beginning immunotherapy treatments involved administration of cytokines such as interleukin with an aim of inducing the lymphocytes to carry on their activity of destroying the tumor cells. This therapy lead to the extraction of the lymphocytes from the blood and culture-expanding them in the lab and then injecting the cells alone to enable them to destroy the cancer cells.
Dendritic cell (DC) therapy represents a new and promising immunotherapeutic approach for treatment of advanced cancer as well as for secondary prevention of cancer. As Dr. Harmon Eyre, the VP of Research at the AMA commented on results of DC therapy for cancer: “Patients’ responses are far out of proportion to anything that any current therapy could do”.
For decades, cancer researchers have been interested in immunologic treatment using vaccines against cancer but with little progress. However, recent breakthroughs have shown that tumor-associated antigens can be used to vaccinate patients and that the dendritic cell is a potent blood cell able to present such antigens and stimulate the naïve immune system.
Dendritic cell therapy has reported success even in stage IV cancer patients who have failed all other therapies.
Another approach to cancer therapy takes advantage of the normal role of the dendritic cell as an immune educator. Dendritic cells grab antigens from viruses, bacteria, or other organisms and wave them at T cells to recruit their help in an initial T cell immune response.
This works well against foreign cells that enter the body, but cancer cells often evade the self/non-self detection system. By modifying dendritic cells, researchers are able to trigger a special kind of autoimmune response that includes a T cell attack of the cancer cells.
Because a cancer antigen alone is not enough to rally the immune troops, scientists first fuse a cytokine to a tumor antigen with the hope that this will send a strong antigenic signal.
Next, they grow a patient’s dendritic cells in the incubator and let them take up this fused cytokine-tumor antigen. This enables the dendritic cells to mature and eventually display the same tumor antigens as appear on the patient’s cancer cells. When these special mature dendritic cells are given back to the patient, they wave their newly acquired tumor antigens at the patient’s immune system, and those T cells that can respond mount an attack on the patient’s cancer cells.
Natural Killer Cells
NK cells are a type of cytotoxic lymphocyte that constitutes a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. They kill cells by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis.
Natural killer (NK) cells have been at the forefront of immunology for two decades. During that time, a great amount of information about these cells has been obtained. They are important in anti-infectious and antitumor defense and shape the adaptive immune response. In addition, they can act as immuno-regulatory cells. In recent years, the therapeutic potential of NK cells in cancer immunotherapy has become increasingly evident.
Despite the wide variety of functions exhibited by mature peripheral blood cells, all are derived from a small pool (1–3%) of primitive precursor cells in the bone marrow (BM) that bear a unique surface glycoprotein, CD34.
Isolated CD34+ cells are capable of reconstituting all hematopoietic lineages, both in experimental animals and in humans following intensive therapy. CD34+ cells capable of reconstituting hematopoiesis are also found at low frequency in peripheral blood (PB), a frequency which can be dramatically increased by combinations of chemotherapy and recombinant cytokines. In some cases, PB “stem cells” (PBSC) can be used to augment or even replace conventional BM autografts. The availability of CD34 antibodies has greatly aided the development of techniques for the enrichment of primitive progenitor cells, thus allowing studies of the hematopoietic potential of stem cells in vitro. Additionally, the use of CD34 antibodies for the “positive selection” of hematopoietic stem/progenitor cells from tumor-contaminated marrow may possibly represent an alternative “purging” strategy prior to transplantation. The availability of pure populations of the most primitive hematopoietic progenitor cells will also facilitate study of genetic manipulation as a practical therapeutic modality.