Synthetic immunology

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Synthetic immunology is the rational design and construction of synthetic systems that perform complex immunological functions. [1] Functions include using specific cell markers to target cells for destruction and or interfering with immune reactions. [2] US Food and Drug Administration (FDA)-approved immune system modulators include anti-inflammatory and immunosuppressive agents, vaccines, therapeutic antibodies and Toll-like receptor (TLR) agonists. [1]

Contents

History

The discipline emerged after 2010 following the development of genome editing technology including TALENS and CRISPR. In 2015, one project created T cells that became active only in the presence of a specific drug, allowing them to be turned on and off in situ. Another example is a T cell that targets only cells that display two separate markers. [3]

In 2016, John Lin head of Pfizer's San Francisco biotech unit stated, “the immune system will be the most convenient vehicle for [engineered human cells], because they can move and migrate and play such important roles.” [3]

Advances in systems biology support high-dimensional quantitative analysis of immune responses. [4] Techniques include viral gene delivery, inducible gene expression, RNA-guided genome editing, and site-specific recombinases for applications related to biotechnology and cellular immunotherapy. [5]

Types

Immunity-modulating organisms

Researchers are exploring the creation of 'smart' organisms such as bacteriophages and bacteria that can perform complex immunological tasks. Such strategies could produce organisms that perform multistep immune functions such as presenting antigen to and co-stimulating helper T cells in a specific manner, or providing integrated signals to B cells to induce affinity maturation and isotype switching during antibody production. Such engineered organisms have the potential be as safe and as inexpensive as probiotics but precise in carrying out targeted interventions. [1]

Antibody-recruiting small molecules

Antibody therapeutics and other 'biologics' have proven to be effective in treating a diseases from rheumatoid arthritis to cancer. However, such agents can cause unwanted anaphylactic or inflammatory reactions, are administered by injection and are expensive. Small molecules, in contrast, are generally inexpensive to produce, orally bioavailable and are rarely allergenic. Synthetic antibody-recruiting small molecules have been created that redirect natural antibodies to pathogens for destruction. [1]

Transdifferentiated cells

Deletion of a single transcription factor enables mature B cells to transform into T cells via dedifferentiation and redifferentiation. Technologies that can control cell fate include strategies to induce pluripotent stem cell formation and using small molecules to induce stem cells to differentiate into specific cell types. Dedifferentiation could be used to turn autoimmune cells into inactive progenitors or to suppress rejection of transplanted organs. [1]

In 2016 researchers transdifferentiated fibroblasts into induced neural stem cells. The team mixed the cells into an FDA-approved surgical glue that provided a physical support matrix. They administered the result to mice. Survival times increased from 160 to 220 percent, depending on the type of tumor. [6] [7]

Vaccines

Therapeutic vaccines treat and immunize patients already infected with a given disease. Provenge is an adoptive cell-transfer therapy in which a patient's antigen-presenting target autologous prostate cancer tissue. Advances in chemical biology include synthetic molecules that modulate B cell activation, structurally complex carbohydrate tumor antigen and adjuvants synthesis, immunogenic chemotherapeutic agents and chemically homogeneous, synthetic vaccines. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

The immune system is a network of biological systems 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.

<span class="mw-page-title-main">Immunology</span> Branch of medicine studying the immune system

Immunology is a branch of biology and medicine that covers the study of immune systems in all organisms.

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

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.

In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.

<span class="mw-page-title-main">Conjugate vaccine</span> Type of vaccine

A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

<span class="mw-page-title-main">Adaptive immune system</span> Subsystem of the immune system

The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

<span class="mw-page-title-main">Virosome</span> Drug or vaccine delivery mechanism

A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane vesicle incorporating virus derived proteins to allow the virosomes to fuse with target cells. Viruses are infectious agents that can replicate in their host organism, however virosomes do not replicate. The properties that virosomes share with viruses are based on their structure; virosomes are essentially safely modified viral envelopes that contain the phospholipid membrane and surface glycoproteins. As a drug or vaccine delivery mechanism they are biologically compatible with many host organisms and are also biodegradable. The use of reconstituted virally derived proteins in the formation of the virosome allows for the utilization of what would otherwise be the immunogenic properties of a live-attenuated virus, but is instead a safely killed virus. A safely killed virus can serve as a promising vector because it won't cause infection and the viral structure allows the virosome to recognize specific components of its target cells.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology 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.

An oncoantigen is a surface or soluble tumor antigen that supports tumor growth. A major problem of cancer immunotherapy is the selection of tumor cell variants that escape immune recognition. The notion of oncoantigen was set forth in the context of cancer immunoprevention to define a class of persistent tumor antigens not prone to escape from immune recognition.

<span class="mw-page-title-main">Trogocytosis</span>

Trogocytosis is when a cell nibbles another cell. It is a process whereby lymphocytes conjugated to antigen-presenting cells extract surface molecules from these cells and express them on their own surface. The molecular reorganization occurring at the interface between the lymphocyte and the antigen-presenting cell during conjugation is also called "immunological synapse".

<span class="mw-page-title-main">Lloyd J. Old</span> 20th-century American immunology researcher

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 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.

Gustav Gaudernack is a scientist working in the development of cancer vaccines and cancer immunotherapy. He has developed various strategies in immunological treatment of cancer. He is involved in several ongoing cellular and immuno-gene therapeutic clinical trials and his research group has put major efforts into the development of various T cell-based immunotherapeutic strategies.

Translational glycobiology or applied glycobiology is the branch of glycobiology and glycochemistry that focuses on developing new pharmaceuticals through glycomics and glycoengineering. Although research in this field presents many difficulties, translational glycobiology presents applications with therapeutic glycoconjugates, with treating various bone diseases, and developing therapeutic cancer vaccines and other targeted therapies. Some mechanisms of action include using the glycan for drug targeting, engineering protein glycosylation for better efficacy, and glycans as drugs themselves.

References

  1. 1 2 3 4 5 6 Spiegel, David A. (2010-12-01). "Grand Challenge Commentary: Synthetic immunology to engineer human immunity". Nature Chemical Biology. 6 (12): 871–872. doi:10.1038/nchembio.477. ISSN   1552-4450. PMID   21079593.
  2. ↑ Geering, Barbara; Fussenegger, Martin (2015-02-01). "Synthetic immunology: modulating the human immune system". Trends in Biotechnology. 33 (2): 65–79. doi:10.1016/j.tibtech.2014.10.006. ISSN   0167-7799. PMID   25466879.
  3. 1 2 Regalado, Antonio (February 2016). "Immune Engineering". MIT Technology Review. Retrieved 2016-02-25.
  4. ↑ Khan TA, Friedensohn S, de Vries ARG, Straszewski J, Ruscheweyh H-J, Reddy ST (2016). "Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting". Sci. Adv. 2 (3): e1501371. Bibcode:2016SciA....2E1371K. doi:10.1126/sciadv.1501371. PMC   4795664 . PMID   26998518.
  5. ↑ "Synthetic Immunology". www.bsse.ethz.ch. ETH Zurich . Retrieved 2016-02-25.
  6. ↑ Lavars, Nick (2016-02-24). "Ordinary skin cells turned into brain tumor predators". www.gizmag.com. Gizmag. Retrieved 2016-02-26.
  7. ↑ Bagó, Juli R.; Alfonso-Pecchio, Adolfo; Okolie, Onyi; Dumitru, Raluca; Rinkenbaugh, Amanda; Baldwin, Albert S.; Miller, C. Ryan; Magness, Scott T.; Hingtgen, Shawn D. (2016-02-02). "Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma". Nature Communications. 7: 10593. Bibcode:2016NatCo...710593B. doi:10.1038/ncomms10593. PMC   4740908 . PMID   26830441.
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