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In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell, consisting mostly of natural killer, natural killer T, and T cells that has been stimulated to kill tumor cells, but because of the function in which they activate, and the cells they can successfully target, they are classified as different than the classical natural killer and T lymphocyte systems.
It has been shown that when Peripheral blood leukocytes (PBL) are cultured in the presence of Interleukin 2, it results in the development of effector cells, which are cytotoxic and are seen to localize to tumor sites and are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic [1] . LAK cells respond to these lymphokines, particularly IL-2, by developing into effector cells capable of lysing tumor cells that are known to be resistant to NK cell activity. After stimulated by IL-2, LAK cells can target and kill tumor cells in the early innate response. [2]
The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot. LAK cells are also capable of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors. LAK cells function in the same way as NK cells in the peripheral blood but are more sensitive to and can target tumor cells.
The use of lymphokine activated killer cells has been found to be helpful in treating human cells with different cancers in vitro [3] . LAK cell therapy is a method that uses interleukin 2 (IL-2) to enhance the number of lymphocytes in an in vitro setting, and it has formed the foundation of many immunotherapy assays that are now in use [4] . LAK cells have shown potential as a cellular agent for cancer therapy and have been utilized therapeutically in association with IL-2 for the treatment of various cancers. LAK cells have anticancer efficacy against homologous carcinoma cells and can grow ex vivo in the presence of IL-2 [5] . In melanoma and gastric cancer cells, intercellular adhesion molecule 1 (ICAM-1) antibody can significantly inhibit in vitro LAK-induced lysis of cancer cells. A study has shown that ICAM1 in lung cancer cells increases LAK cell-mediated tumor cell death as a new anti-tumor mechanism [6] . One study uses a 4 hour chromium release assay, which is an assay used to measure the cytotoxicity of T cells and natural killer cells, to measure lysis of the fresh solid tumor cells from 10 cancer patients and found that in all 10 cancer patients the fresh autologous tumor cells were resistant to lysis by PBL with natural killer cells, but were lysed by the LAK cells. [7]
LAK cells, along with the administration of IL-2 have been experimentally used to treat cancer in mice and humans, but there is very high toxicity with this treatment - Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Treatment of IL-2 cells by themselves to treat cancers are more dangerous than treatment with the combination of IL-2 and LAK cells. [8]
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Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.
This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, helper T cells and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.
Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system kills a target cell, whose membrane-surface antigens have been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection.
Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.
Interleukin 21 (IL-21) is a protein that in humans is encoded by the IL21 gene.
CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.
Gamma delta T cells are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, γδ T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells. Their highest abundance is in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).
Natural cytotoxicity triggering receptor 3 is a protein that in humans is encoded by the NCR3 gene. NCR3 has also been designated as CD337 and as NKp30. NCR3 belongs to the family of NCR membrane receptors together with NCR1 (NKp46) and NCR2 (NKp44).
CD226, PTA1 or DNAM-1 is a ~65 kDa immunoglobulin-like transmembrane glycoprotein expressed on the surface of natural killer cells, NK T cell, B cells, dendritic cells, hematopoietic precursor cells, platelets, monocytes and T cells.
The Interleukin-2 receptor alpha chain is a protein involved in the assembly of the high-affinity Interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with Interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.
Autologous immune enhancement therapy (AIET) is a treatment method in which immune cells are taken out from the patient's body which are cultured and processed to activate them until their resistance to cancer is strengthened and then the cells are put back in the body. The cells, antibodies, and organs of the immune system work to protect and defend the body against not only tumor cells but also bacteria or viruses.
ALECSAT technology is a novel method of epigenetic cancer immunotherapy being used by the company CytoVac. It uses a patient's own immune system to target tumor cells in prostate cancer, glioblastomas, and potentially pancreatic cancer. ALECSAT research, directed by Alexei Kirken and Karine Dzhandzhugazyan, has led to several clinical trials.
The NK-92 cell line is an immortalised cell line that has the characteristics of a type of immune cell found in human blood called ’natural killer’ (NK) cells. Blood NK cells and NK-92 cells recognize and attack cancer cells as well as cells that have been infected with a virus, bacteria, or fungus. NK-92 cells were first isolated in 1992 in the laboratory of Hans Klingemann at the British Columbia Cancer Agency in Vancouver, Canada, from a patient who had a rare NK cell non-Hodgkin-lymphoma. These cells were subsequently developed into a continuously growing cell line. NK-92 cells are distinguished by their suitability for expansion to large numbers, ability to consistently kill cancer cells and testing in clinical trials. When NK-92 cells recognize a cancerous or infected cell, they secrete perforin that opens holes into the diseased cells and releases granzymes that kill the target cells. NK-92 cells are also capable of producing cytokines such as tumor necrosis factor alpha (TNF-a) and interferon gamma (IFN-y), which stimulates proliferation and activation of other immune cells.
Immunoediting is a dynamic process that consists of immunosurveillance and tumor progression. It describes the relation between the tumor cells and the immune system. It is made up of three phases: elimination, equilibrium, and escape.
Cytokine-induced killer cells (CIK) cells are a group of immune effector cells featuring a mixed T- and natural killer (NK) cell-like phenotype. They are generated by ex vivo incubation of human peripheral blood mononuclear cells (PBMC) or cord blood mononuclear cells with interferon-gamma (IFN-γ), anti-CD3 antibody, recombinant human interleukin (IL)-1 and recombinant human interleukin (IL)-2.
Thomas A. Waldmann was an American immunologist who has worked on therapeutic monoclonal antibodies to the IL-2 receptor, Interleukin 15 (IL-15), and Adult T-cell Leukemia (ATL). Until the week he died, he was an active distinguished investigator at the Lymphoid Malignancies Branch of the National Cancer Institute.
Cellular adoptive immunotherapy is a type of immunotherapy. Immune cells such as T-cells are usually isolated from patients for expansion or engineering purposes and reinfused back into patients to fight diseases using their own immune system. A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. The primary types of cellular adoptive immunotherapies are T cell therapies. Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy.