Immunotherapy
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Immunotherapy | |
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MeSH | D007167 |
OPS-301 code | 8-03 |
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.[1][2][3][4]
Cell-based immunotherapies are effective for some cancers.[5][6] Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells, and cytotoxic T lymphocytes work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of tumor cells. Vaccine-induced immunity to COVID-19 relies mostly on an immunomodulatory T-cell response.[7]
Therapies such as
Immunomodulators
Immunomodulators are the active agents of immunotherapy. They are a diverse array of recombinant, synthetic, and natural preparations.[8]
Class | Example agents |
---|---|
Interleukins |
IL-2, IL-7, IL-12 |
Cytokines |
G-CSF
|
Chemokines |
CCL3, CCL26, CXCL7 |
Immunomodulatory imide drugs (IMiDs) |
thalidomide and its analogues (lenalidomide, pomalidomide, and apremilast), BCG vaccine,[9][10] & Covid vaccines[11][12][7] |
Other | cytosine phosphate-guanosine, oligodeoxynucleotides, glucans
|
Activation immunotherapies
Cancer
Cancer treatment used to be focused on killing or removing cancer cells and tumours, with chemotherapy or surgery or radiation. These treatments can be very effective and in many cases are still used. In 2018 the Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation." Cancer immunotherapy attempts to stimulate the immune system to destroy tumours. A variety of strategies are in use or are undergoing research and testing. Randomized controlled studies in different cancers resulting in significant increase in survival and disease free period have been reported[2] and its efficacy is enhanced by 20–30% when cell-based immunotherapy is combined with conventional treatment methods.[2]
One of the oldest forms of cancer immunotherapy is the use of BCG vaccine, which was originally to vaccinate against tuberculosis and later was found to be useful in the treatment of bladder cancer.[13] BCG immunotherapy induces both local and systemic immune responses. The mechanisms by which BCG immunotherapy mediates tumor immunity have been widely studied, but they are still not completely understood.[14]
The use of monoclonal antibodies in cancer therapy was first introduced in 1997 with rituximab, an anti-CD20 antibody for treatment of B cell lymphoma.[15] Since then several monoclonal antibodies have been approved for treatment of various haematological malignancies as well as for solid tumours.[16][17]
The extraction of
Adoptive cell transfer has been tested on lung[27] and other cancers, with greatest success achieved in melanoma.
Dendritic cell-based pump-priming or vaccination
The current approaches for
T-cell adoptive transfer
Adoptive cell transfer in vitro cultivates autologous, extracted T cells for later transfusion.[32]
Alternatively,
Whether T cells are genetically engineered or not, before re-infusion, lympho-depletion of the recipient is required to eliminate regulatory T cells as well as unmodified, endogenous lymphocytes that compete with the transferred cells for homeostatic cytokines.[32][38][39][40] Lymphodepletion may be achieved by myeloablative chemotherapy, to which total body irradiation may be added for greater effect.[41] Transferred cells multiplied in vivo and persisted in peripheral blood in many people, sometimes representing levels of 75% of all CD8+ T cells at 6–12 months after infusion.[42] As of 2012[update], clinical trials for metastatic melanoma were ongoing at multiple sites.[43] Clinical responses to adoptive transfer of T cells were observed in patients with metastatic melanoma resistant to multiple immunotherapies.[44]
Checkpoint inhibitors
Although these molecules were originally discovered as molecules playing a role in
Immune checkpoint inhibitors are approved to treat some patients with a variety of cancer types, including melanoma, breast cancer, bladder cancer, cervical cancer, colon cancer, head and neck cancer, or Hodgkin lymphoma.[47]
These therapies have revolutionized cancer immunotherapy as they showed for the first time in many years of research in metastatic melanoma, which is considered one of the most immunogenic human cancers, an improvement in overall survival, with an increasing group of patients benefiting long-term from these treatments.[46]
Immune enhancement therapy
Suppression immunotherapies
Immunosuppressive drugs
Immunosuppressive drugs help manage organ transplantation and autoimmune disease. Immune responses depend on lymphocyte proliferation. Cytostatic drugs are immunosuppressive. Glucocorticoids are somewhat more specific inhibitors of lymphocyte activation, whereas inhibitors of immunophilins more specifically target T lymphocyte activation. Immunosuppressive antibodies target steps in the immune response. Other drugs modulate immune responses and can be used to induce immune regulation. It has been observed in a preclinical trial that regulation of the immune system by small immunosuppressive molecules such as vitamin D, dexamethasone, and curcumin administered under a low-dose regimen and subcutaneously, could be helpful in preventing or treating chronic inflammation.[55][56]
Immune tolerance
The body naturally does not launch an immune system attack on its own tissues. Models generally identify
Creating immune tolerance reduces or eliminates the need for lifelong immunosuppression and attendant side effects. It has been tested on transplantations, rheumatoid arthritis, type 1 diabetes and other autoimmune disorders.
Modality | Details | ||
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Non-antigen specific | Monoclonal Antibodies |
Depleting: |
Non-depleting:
|
Haematopoietic stem cell transplantation | Non-myeloablative | Myeloablative | |
Mesenchymal stem cell transplantation | |||
Regulatory T cell therapy | Non-antigen specific | Antigen-specific | |
Low dose IL-2 to expand regulatory T cells | |||
Microbiome manipulation | |||
Antigen specific | Peptide therapy | Subcutaneous, intradermal, transmucosal (oral, inhaled)
Tolerogenic dendritic cells, liposomes and nanoparticles | |
Altered peptide ligands |
Allergen Immunotherapy
Immunotherapy can also be used to treat
Immunotherapy may produce long-term benefits.[63] Immunotherapy is partly effective in some people and ineffective in others, but it offers people with allergies a chance to reduce or stop their symptoms.[citation needed]
The therapy is indicated for people who are extremely allergic or who cannot avoid specific allergens.
A promising approach to treat food allergies is the use of
Helminthic therapies
Co-evolution with helminths has shaped some of the genes associated with
See also
- Biological response modifier
- Sepsivac
- Checkpoint inhibitor
- Interleukin-2 immunotherapy
- Immunostimulant
- Microtransplantation
- Photoimmunotherapy in vitro or in vivo[79][80][81][82][83][84][85]
References
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