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In immunology, an antigen (Ag) is any molecule, molecular structure, foreign particulate matter, or pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. Antigens can be proteins, peptides, polysaccharides, lipids, or nucleic acids.
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
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 known 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.
A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno", in reference to antibodies used in the procedure, and "histo", meaning tissue. Albert Coons conceptualized and first implemented the procedure in 1941.
Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8+ T cells into activated cytotoxic CD8+ T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.
Understanding of the antitumor immunity role of CD4+ T cells has grown substantially since the late 1990s. CD4+ T cells (mature T-helper cells) play an important role in modulating immune responses to pathogens and tumor cells, and are important in orchestrating overall immune responses.
Antigenic escape, immune escape, immune evasion or escape mutation occurs when the immune system of a host, especially of a human being, is unable to respond to an infectious agent: the host's immune system is no longer able to recognize and eliminate a pathogen, such as a virus. This process can occur in a number of different ways of both a genetic and an environmental nature. Such mechanisms include homologous recombination, and manipulation and resistance of the host's immune responses.
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.
A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for cancer immunotherapy, drug delivery, and Alzeimer's disease.
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.
Cancer immunoprevention is the prevention of cancer onset with immunological means such as vaccines, immunostimulators or antibodies. Cancer immunoprevention is conceptually different from cancer immunotherapy, which aims at stimulating immunity in patients only after tumor onset, however the same immunological means can be used both in immunoprevention and in immunotherapy.
Vaccine therapy is a type of treatment that uses a substance or group of substances to stimulate the immune system to destroy a tumor or infectious microorganisms such as bacteria or viruses.
Lloyd John Old was one of the founders and standard-bearers of the field of cancer immunology. When Old began his career in 1958, tumor immunology was in its infancy. Today, cancer immunotherapies are emerging as a significant advance in cancer therapy.
Active immunotherapy is a type of immunotherapy that aims to stimulate the host's immune system or a specific immune response to a disease or pathogen and is most commonly used in cancer treatments. Active immunotherapy is also used for treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Active immunotherapies induce an immune response through direct immune system stimulation, while immunotherapies that administer antibodies directly to the system are classified as passive immunotherapies. Active immunotherapies can elicit generic and specific immune responses depending on the goal of the treatment. The categories of active immunotherapy divide into:
Peptide-based synthetic vaccines, also called epitope vaccines, are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.
Imugene Ltd is a biotechnology company working in cancer immunotherapy. The company's lead product is HER-Vaxx, a therapeutic cancer vaccine for the treatment of gastric cancer and breast cancer, where the cancer is HER-2-positive. Imugene was planning a Phase Ib/II clinical study of HER-Vaxx in gastric cancer which it intended to initiate in 2016. Imugene stock is publicly traded on the Australian Securities Exchange (ASX).
Ursula Wiedermann is an Austrian medical scientist who has made significant contributions in the field of allergies and of cancer immunotherapy. She is currently Professor of Vaccinology at the Medical University of Vienna. Wiedermann's work in the field of B cell peptide vaccines led to the creation of HER-Vaxx, an immunotherapy for the treatment of HER-2-positive cancers. This vaccine is currently being taken into mid-stage clinical development in gastric cancer by the biotech company Imugene, where Wiedermann is Chief Scientific Officer.
Cancer vaccine targeting CD4+ T cells is a type of vaccine used to treat existing cancer. Cancerous cells usually cannot be recognized by the human immune system, and therefore cannot be destroyed. Some researchers state that cancer can be treated by increasing the response of T cells, especially CD4+ T cells, to cancerous cells through cancer vaccine injection.
Whole-cell vaccines are a type of vaccine that has been prepared in the laboratory in such a way to express immune cells such as cytokines, chemokines and other costimulatory molecules. When administered to the patients, these molecules will stimulate the immune system of the patient. The whole-cell vaccine simultaneously targets multiple antigens to activate the immune system and induces antigen-specific T-cell responses.
References
- ↑ Lollini PL, Cavallo F, Nanni P, Forni G (March 2006). "Vaccines for tumour prevention". Nat. Rev. Cancer. 6 (3): 204–16. doi:10.1038/nrc1815. PMID 16498443. S2CID 41804071.
- ↑ Lollini PL, Forni G (February 2003). "Cancer immunoprevention: tracking down persistent tumor antigens". Trends Immunol. 24 (2): 62–6. doi:10.1016/S1471-4906(02)00030-3. PMID 12547501.
- ↑ García-Lora A, Algarra I, Collado A, Garrido F (June 2003). "Tumour immunology, vaccination and escape strategies". Eur. J. Immunogenet. 30 (3): 177–83. doi:10.1046/j.1365-2370.2003.00384.x. PMID 12786993.
- ↑ Nanni P, Nicoletti G, De Giovanni C, et al. (November 2001). "Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice". J. Exp. Med. 194 (9): 1195–205. doi:10.1084/jem.194.9.1195. PMC 2195980 . PMID 11696586.
- ↑ Lollini PL, Nicoletti G, Landuzzi L, De Giovanni C, Nanni P (May 2005). "New target antigens for cancer immunoprevention". Curr Cancer Drug Targets. 5 (3): 221–8. doi:10.2174/1568009053765762. PMID 15892621.
- ↑ Cavallo F, Calogero RA, Forni G (September 2007). "Are oncoantigens suitable targets for anti-tumour therapy?". Nat. Rev. Cancer. 7 (9): 707–13. doi:10.1038/nrc2208. PMID 17700704. S2CID 2491531.