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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
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Cell-based immunotherapies are effective for some cancers. Immune effector cells such as , , , 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.
Therapies such as granulocyte colony-stimulating factor (G-CSF), , imiquimod and cellular membrane fractions from bacteria are licensed for medical use. Others including IL-2, IL-7, IL-12, various , synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and are involved in clinical and preclinical studies.
| IL-2, IL-7, IL-12 |
| , G-CSF |
| CCL3, CCL26, CXCL7 |
| thalidomide and its analogues (lenalidomide, pomalidomide, and apremilast), BCG vaccine, & Covid vaccines |
| cytosine phosphate-guanosine, oligodeoxynucleotides, glucans |
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. 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.
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. Since then several monoclonal antibodies have been approved for treatment of various haematological malignancies as well as for solid tumours.
The extraction of G-CSF lymphocytes from the blood and expanding in vitro against a tumour antigen before reinjecting the cells with appropriate stimulatory cytokines. The cells then destroy the tumour cells that express the antigen. Topical immunotherapy utilizes an immune enhancement cream (imiquimod) which produces interferon, causing the recipient's killer T cells to destroy , actinic keratoses, basal cell cancer, vaginal intraepithelial neoplasia, squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma. Injection immunotherapy ("intralesional" or "intratumoural") uses mumps, candida, the HPV vaccine or trichophytin antigen injections to treat warts (HPV induced tumours).
Adoptive cell transfer has been tested on Lung cancer and other cancers, with greatest success achieved in melanoma.
The current approaches for DC-based vaccination are mainly based on antigen loading on in vitro-generated DCs from or CD34+ cells, activating them with different TLR ligands, cytokine combinations, and injecting them back to the patients. The in vivo targeting approaches comprise administering specific cytokines (e.g., Flt3L, GM-CSF) and targeting the DCs with antibodies to C-type lectin receptors or agonistic antibodies (e.g., anti-CD40) that are conjugated with antigen of interest. Multiple, next-generation anti-CD40 platforms are being actively developed. Future approach may target DC subsets based on their specifically expressed C-type lectin receptors or chemokine receptors. Another potential approach is the generation of genetically engineered DCs from induced pluripotent stem cells and use of neoantigen-loaded DCs for inducing better clinical outcome.
The first proof-of-concept for ACT was demonstrated by Steven Rosenberg and colleagues in 1988, when they showed that TILs expanded ex vivo and reinfused into patients, together with high-dose interleukin-2, could mediate tumor regression in patients with metastatic melanoma. In 2024, FDA has granted an accelerated approval for lifileucel, a TIL-based therapy for metastatic melanoma.
Adoptive cell transfer in vitro cultivates autologous, extracted T cells for later transfusion.
Alternatively, Genetically engineered T cells are created by harvesting T cells and then infecting the T cells with a retrovirus that contains a copy of a T cell receptor (TCR) gene that is specialised to recognise tumour antigens. The virus integrates the receptor into the T cells' genome. The cells are expanded non-specifically and/or stimulated. The cells are then reinfused and produce an immune response against the tumour cells. The technique has been tested on refractory stage IV metastatic melanomas and advanced skin cancer. In 2024, the FDA granted accelerated approval to afamitresgene autoleucel (TECELTA, Adaptimmune LLC), the first TCR-T therapy for solid tumors.
CAR-T therapy uses peripheral blood T cells that are genetically engineered ex vivo to express synthetic receptors targeting specific tumor antigens. To date, the FDA has approved several CAR-T cell therapies for hematological malignancies, including B-cell acute lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma. The first FDA-approved CAR-T therapy, Kymriah, used this approach. To obtain the clinical and commercial supply of this CAR-T, Novartis purchased the manufacturing plant, the distribution system and hired the production team that produced Sipuleucel-T developed by Dendreon and the Immune Response Corporation.
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. Lymphodepletion may be achieved by myeloablative chemotherapy, to which total body irradiation may be added for greater effect. 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. , clinical trials for metastatic melanoma were ongoing at multiple sites. Clinical responses to adoptive transfer of T cells were observed in patients with metastatic melanoma resistant to multiple immunotherapies.
Although these molecules were originally discovered as molecules playing a role in T cell activation or apoptosis, subsequent preclinical research showed their important role in the maintenance of peripheral immune tolerance. (2025). 9783318055894 ISBN 9783318055894
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, lung cancer head and neck cancer, or Hodgkin lymphoma.
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 Immunogenicity human cancers, an improvement in overall survival, with an increasing group of patients benefiting long-term from these treatments, although caution remains needed for specific subgroups. (2025). 9783030793074 ISBN 9783030793074
The next generation of checkpoint inhibitors targets other receptors such as lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT). Antibodies against these receptors have been evaluated in clinical studies, but have not yet been approved for widespread use.
Immune tolerance therapies seek to reset the immune system so that the body stops mistakenly attacking its own organs or cells in autoimmune disease or accepts foreign tissue in . A recent therapeutic approach is the infusion of regulatory immune cells into transplant recipients. The transfer of regulatory immune cells has the potential to inhibit the activity of effector. (2025). 9781493989362 ISBN 9781493989362
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.
Subcutaneous allergen immunotherapy was first introduced in 1911 through the hypothesis that people with hay fever were sensitive to pollen from grass. A process was developed to create an extract by drawing out timothy pollen in distilled water and then boiling it. This was injected into patients in increasing doses to help alleviate symptoms.
Allergen Immunotherapy is indicated for people who are extremely allergic or who cannot avoid specific and when there is evidence of an IgE-mediated reaction that correlates with allergen symptoms. These IgE-mediated reactions can be identified via a blood IgE test or skin testing. If a specific IgE antibody is negative, there is no evidence that allergen immunotherapy will be effective for that patient.
However, there are risks associated with allergen immunotherapy as it is the administration of an agent the patient is known to be highly allergic to. Patients are at increased risk of fatal anaphylaxis, local reaction at the site of injection, or life-threatening systemic allergic reactions.
A promising approach to treat food allergies is the use of oral immunotherapy (OIT). OIT consists in a gradual exposure to increasing amounts of allergen can lead to the majority of subjects tolerating doses of food sufficient to prevent reaction on accidental exposure. Dosages increase over time, as the person becomes desensitized. This technique has been tested on infants to prevent peanut allergies.
Co-evolution with helminths has shaped some of the genes associated with interleukin expression and immunological disorders, such Crohn's, ulcerative colitis and Coeliac disease. Helminths' relationship to humans as hosts should be classified as mutualistic or symbionts. In some ways, the relationship is symbiotic because the worms themselves need the host (humans) for survival, because this body supplies them with nutrients and a home. From another perspective, it could be reasoned that it is mutualistic, being that the above information about benefits in autoimmune disorders continues to remain true and supported. Also, some say that the worms can regulate gut bacteria. Another possibility is one of this being a parasitic relationship, arguing that the possible risks of anemia and other disorders outweighs the benefits, yet this is significantly less supported, with the research alluding to the mutualistic and symbiotic approach being much more likely.
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