Immunotherapy, also known as biological therapy or biotherapy, encompasses a diverse set of therapeutic strategies that harness or modify the immune system to prevent, control, or eliminate disease. In its narrowest definition, immunotherapy refers to treatments designed to stimulate or guide the immune system to recognize and fight cancer, often by enhancing or restoring immune responses to eradicate malignant cells while sparing healthy tissue. A broader definition of immunotherapy applies beyond oncology, including strategies to stimulate or suppress immune activity against other diseases such as autoimmune disorders, infectious diseases, and allergies. These approaches may involve vaccines, immune modulators, or monoclonal antibodies designed to alter immune responses, either to boost protection against pathogens or to reduce damaging inflammation. Immunotherapy includes both passive methods, like monoclonal antibodies that mark abnormal cells for immune destruction, and active methods, such as cancer vaccines, immune checkpoint inhibitors, adoptive cell transfer, and cytokine therapies. Advances in immunotherapy have transformed the treatment landscape for cancer and are increasingly applied to a wider range of conditions, improving outcomes for many patients, though responses can vary depending on disease type, genetic background, and environmental factors. Cell-based immunotherapies are effective for some cancers. 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. Therapies such as granulocyte colony-stimulating factor (G-CSF), interferons, imiquimod and cellular membrane fractions from bacteria are licensed for medical use. Others including IL-2, IL-7, IL-12, various chemokines, synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and glucans are involved in clinical and preclinical studies.
Immunomodulators Immunomodulators are the active agents of immunotherapy. They are a diverse array of recombinant, synthetic, and natural preparations.
Activation immunotherapies
Cancer
Cancer treatment used to be focused on killing or removing cancer cells and tumours, with chemotherapy or surgery or radiation. 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 and its efficacy is enhanced by 20–30% when cell-based immunotherapy is combined with conventional treatment methods. 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 warts, actinic keratoses, basal cell cancer, vaginal intraepithelial neoplasia, squamous cell cancer, cutaneous lymphoma, and superficial 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 and other cancers, with greatest success achieved in melanoma.
Dendritic cell-based pump-priming or vaccination Dendritic cells (DC) can be stimulated to activate a cytotoxic response towards an antigen. Dendritic cells, a type of antigen-presenting cell, are harvested from the person needing the immunotherapy. These cells are then either pulsed with an antigen or tumour lysate or transfected with a viral vector, causing them to display the antigen. Upon transfusion into the person, these activated cells present the antigen to the effector lymphocytes (CD4+ helper T cells, cytotoxic CD8+ T cells and B cells). This initiates a cytotoxic response against tumour cells expressing the antigen (against which the adaptive response has now been primed). The first FDA-approved cell-based immunotherapy, the cancer vaccine Sipuleucel-T is one example of this approach. The Immune Response Corporation (IRC) developed this immunotherapy and licensed the technology to Dendreon, which obtained FDA clearance. The current approaches for DC-based vaccination are mainly based on antigen loading on in vitro-generated DCs from monocytes 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.
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