Immunotherapy is through the body's own immune system to attack cancer cells to achieve the purpose of cancer treatment, it has become in addition to traditional chemotherapy, radiotherapy and targeted therapy other than the new cancer treatment, and the advantages are obvious. And what role does cytokine play in immunotherapy?
- Type of immunotherapy -
1. Non-specific immunotherapy
Phagocytic cells, NK cells can secrete a variety of cytokines, such as interleukin (IL), interferon (IFN), granulocyte - colony stimulating factor (GM-CSF) and so on. Directly related to the relevant cytokines may play a role in regulating immune cell activation and proliferation. Several recombinant cytokines are currently approved by the US Food and Drug Administration (FDA) for anti-tumor immune stimulants such as IFN-α2a, IFN-α2b and IL-2. In addition, GM-CSF is also clinically used as an immunoconstrictor for transplanted patients or cancer patients after chemotherapy.
2. Tumor vaccine
In 2010, the US Food and Drug Administration (FDA) approved the use of the sipuleucel-T vaccine for asymptomatic or symptomatic metastatic steroid-resistant prostate cancer, a sign that cancer vaccines are moving from basic research to clinical use.3. adoptive immune cell therapy
That is, autoimmune cell therapy technology. This refers to the in vitro activation of autologous or allogeneic immune effector cells infused to the patient, the purpose is to kill the patient's tumor cells. This is also the lung cancer wise choice consensus involved in the immune cell treatment part. "Since the mid-80s of the last century, the rise of cellular biotherapy, almost all diseases have received autologous blood transfusion of lymphokine-activated killer cells (LAK cells) treatment, and in 2008 the technology and 'face-lift' appears, the name replaced "Cytokine-induced killer cells (CIK) immunotherapy." Today, this technology is widely developed throughout the country, but prospective, retrospective clinical studies can not provide sufficient evidence to support it. Clinical trials (Clincal Trials) site after the search conducted a search, found that the world CIK immunotherapy for lung cancer only in China, and China has only eight studies registered in this site.
3. adoptive immune cell therapy
That is, autoimmune cell therapy technology. This refers to the in vitro activation of autologous or allogeneic immune effector cells infused to the patient, the purpose is to kill the patient's tumor cells. This is also the lung cancer wise choice consensus involved in the immune cell treatment part. "Since the mid-80s of the last century, the rise of cellular biotherapy, almost all diseases have received autologous blood transfusion of lymphokine-activated killer cells (LAK cells) treatment, and in 2008 the technology and 'face-lift' appears, the name replaced "Cytokine-induced killer cells (CIK) immunotherapy." Today, this technology is widely developed throughout the country, but prospective, retrospective clinical studies can not provide sufficient evidence to support it. Clinical trials (Clincal Trials) site after the search conducted a search, found that the world CIK immunotherapy for lung cancer only in China, and China has only eight studies registered in this site.
4. Monoclonal antibody
There are dozens of monoclonal antibodies that have been approved for use in cancer therapy, including targeted therapies such as trastuzumab, cetuximab and rituximab, which are well known, and are currently of concern The immune targeting therapy associated with death receptor 1 (PD-1) and its ligand 1 (PD-L1) is also of this interest.
- The common cytokine mechanism in immune cell therapy research -
Interleukin 1 (IL-1α, IL-1β):
IL-1α and IL-1β are encoded by different genes that share the same receptor in vivo and have the same biological activity. IL-1 can stimulate the proliferation of CD4 + T cells in vitro, induce IL-2 production, co-stimulate CD8 + / IL1R + T cell activation, and stimulate mature B cell proliferation and immunoglobulin secretion.
When IL-1α and IFN-γ and activated CD3 monoclonal antibody combined, can significantly improve the cytotoxic effect of CIK.
Interleukin 2 (IL-2):
Interleukin 2 is widely used to promote the activation and proliferation of T cells and NK cells. Interleukin 2 can stimulate NK cell proliferation, increase cytotoxicity and stimulate NK cells to secrete a variety of cytokines.
One drawback of IL2-activated T cells is the ability to activate CD4 + FoxP3 Treg regulatory cells. Treg can inhibit T cell activation and tumor killing. Second, interleukin 2 can also induce activated T cell apoptosis. IL-2 also causes excessive differentiation of T cells, the formation of weak anti-aging aging T cells. The current view of IL2 is that it is a T cell regulator rather than a pure activator. So gradually have been replaced by other IL-like IL7, IL15, IL21 and other trends.
Interleukin 4 (IL-4):
IL-4 regulates the growth of macrophages and guides the differentiation of monocytes into DC. Mononuclear cells will differentiate into macrophages when IL-4 is not added in the culture system. At the same time, IL-4 also reduces the expression of CD14 molecules on the cell surface. The reduction of CD14 expression level is an important marker of monocyte differentiation into DC.
IL-5, IL-6, IL-10 and IL-6, IL-6, IL-6, IL-6, IL-6, IL-6, IL-6, IL-6, IL-6, IL-6, IL-6 -13. It also plays a key role in regulating humoral immunity and adaptive immunity, inducing the conversion of B cell antibody classes to IgE, upregulating MHC II production.
IL-4 and GM-CSF can differentiate into mononuclear cells into immature DC (immature DC). At this time, DC has strong antigen uptake and processing ability, but the ability of antigen presentation is weak. It is therefore recommended to use DC-α in order to promote DC maturation.
IL12 can specifically induce the differentiation of Th1 relative to the specific effect of IL4 on Th2, and thus maintain long-term antitumor activity and become more and more widely used in in vitro cell culture.
Interleukin 7 (IL-7):
Interleukin 7 stimulates the survival and proliferation of T cells by sharing the γc receptor subunit with BAI 2. Interleukin 7 can provide continuous stimulatory signals for Naïve T cells and memory T cells. IL7 activates CD8 + T cells without activating CD4 + FoxP3 + Treg cells relative to IL2 function. In mouse models, IL7 stimulates the proliferation of antigen-specific T cells and is used in two clinical trials. Another clinical application of Bai Jie 7 is used to restore the number of T cells after chemotherapy or hematopoietic stem cell transplantation.
Interleukin 15 (IL-15):
Interleukin 15 stimulates the activation and proliferation of T cells by sharing the γc receptor subunit with BAI. The advantage of interleukin 15 in immune cell therapy is that it does not cause activated T cell apoptosis. Another feature of IL15 in immunotherapy is the maintenance of memory T cells, which play an important role in long-term antitumor activity. The anti-tumor properties of Baijie 15 are due to its stimulatory activity against CD8 + T cells, while IL15 activates NK cells, NKT cells and γδT cells.
Interleukin 21 (IL-21):
Interleukin 21, like other members of the white-2 family, exerts its biological function through a specific receptor subunit and IL2 receptor γc subunit complex receptor. A variety of biological effects of IL21 include: promoting the proliferation of CD4 + and CD8 + T cells, enhancing the cytotoxicity of CD8 + T cells and NK cells without causing apoptosis of activated cells.
A significant advantage of IL21 and IL2 is the priority of CD27 + CD28 + CD8 + T cells. It is generally thought that this cell group is "young" T cells with a stronger cytotoxic effect. While IL21 does not cause amplification of Treg. As IL21 in vitro stimulation of antigen-specific T cells to produce and improve the affinity of the excellent effect of antigen, in immune cell therapy has been more and more widely used.
Interleukin 12 (IL-12):
Interleukin 12 is an activated T cell and NK cell growth factor. Promote the differentiation of CD4 + T cells into CD4 + Th1 T cells, and enhance the activity of CD8 + CTLs cells. Bai Jie 12 through a variety of mechanisms to promote immune cell tumor killer activity, its mechanism and dose, time, and other interactions of cytokines and so on. In the mouse anti-melanin model, high doses of IL12 act through NK cells, whereas low doses of IL12 act as tumor killers by NKT.
Interleukin 18 (IL-18):
Interleukin 18 can stimulate NK cells and CD8 + T cells to secrete gamma interferon (IFNγ), and enhance the cytotoxicity of NK cells and CD8 + T cells. Other biological effects of Baizhu 18 include promoting the activation of macrophages, the development of Th1 CD4 + T cells, and promoting the expression of FasL in lymphocytes.
Granulocyte macrophage colony stimulating factor (GM-CSF):
GM-CSF is one of the earliest cytokines found to have a role in DC. The function of GM-CSF in DC culture is to promote the differentiation of monocytes into macrophage-like cells and promote the expression of MHC class II molecules on the cell surface, thereby enhancing the antigen presenting function of cells. In addition, GM-CSF can also promote the survival of DC. GM-CSF exhibits activity to activate the immune response in a variety of tumor models. The anti-tumor activity of GM-CSF is derived from the biological function of activated macrophag
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