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- Lymphokine-Activated+Killer+Cells at the US National Library of Medicine Medical Subject Headings (MeSH)
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In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell that has been stimulated to kill tumor cells. [1] If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells. [2]
It has been shown that lymphocytes, when exposed to Interleukin 2, are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic. [3] LAK cells respond to these lymphokines, particularly IL-2, by lysing tumor cells that were already known to be resistant to NK cell activity. [4]
The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot. [4] 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. [4] LAK cells are specific to tumor cells and do not display activity against normal cells. [4]
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. [5] 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. [6] 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. [7] 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. [8]
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Cytokines are a broad and loose category of small proteins important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Their definite distinction from hormones is still part of ongoing research.
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 that belong to the rapidly expanding family of 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 cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to 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 1. 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.
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. The major sources of IL-2 are activated CD4+ T cells and activated CD8+ T cells.
Cancer immunotherapy is the artificial stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspeciality of oncology.
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 actively lyses 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 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.
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, and macrophages. 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.
Cancer immunology is an interdisciplinary branch of biology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.
Tumor-infiltrating lymphocytes are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of ‘tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells, in variable proportions. Their abundance varies with tumor type and stage and in some cases relates to disease prognosis
Programmed cell death protein 1, also known as PD-1 and CD279, is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.
Siltuximab is a chimeric monoclonal antibody. It binds to interleukin-6. Siltuximab has been investigated for the treatment of neoplastic diseases: metastatic renal cell cancer, prostate cancer, and Castleman's disease, among other types of cancer.
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
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.
Pelareorep is a proprietary isolate of the unmodified human reovirus being developed as a systemically administered immuno-oncological viral agent for the treatment of solid tumors and hematological malignancies. Pelareorep is an oncolytic virus, which means that it preferentially lyses cancer cells. Pelareorep also promotes an inflamed tumor phenotype through innate and adaptive immune responses. Preliminary clinical trials indicate that it may have anti-cancer effects across a variety of cancer types when administered alone and in combination with other cancer therapies.
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.
Shimon Slavin, M.D., is an Israeli professor of medicine. Slavin pioneered the use of immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation for the cure of hematological malignancies and solid tumors, and using hematopoietic stem cells for induction of transplantation tolerance to bone marrow and donor allografts.
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.