Peptide therapy for Type I diabetes: the immunological homunculus and the rationale for vaccination

Ir, Cohen

doi:10.1007/s00125-002-0937-z

Cited by 48 publications

(3 citation statements)

References 59 publications

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“…In addition, advances in peptide manipulations such as synthesis of D-amino acids, cyclic peptides, incorporation of chemicals and nanocarriers have further increased the bioavailability of peptides 53 . Currently, ample examples of efficacious and safe peptide drugs are available in the market 54 - 57 . Great success has been achieved for the peptide drug Fuzeon TM (enfuvirtide), a synthetic peptide that blocks viral fusion by binding to the gp41 (polypeptide chain) of the human immunodeficiency virus (HIV) type-1 envelope protein 55 .…”

Section: Development Of Peptides As Therapeuticsmentioning

confidence: 99%

“…In 2011, 25 of the US-approved peptide drugs accounted for the global sale of over US$14.7 billion, while Victoza®, Zoladex®, Sandostatin®, Lupron® and Copaxone® each had global sales of over US$1,000 million 63 . Some other examples of therapeutic peptides include glucagon-like peptide-1 (GLP-1) and analogues 57 , deletion peptides of insulin 56 and a deletion peptide of the heat shock protein 60 54 that have been used widely in the treatment of diabetes. This has demonstrated the potential and importance of peptides as pharmacological agents.…”

Section: Development Of Peptides As Therapeuticsmentioning

confidence: 99%

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Peptides as Therapeutic Agents for Dengue Virus

Chew

Poh

2017

Int. J. Med. Sci.

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Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

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Section: Development Of Peptides As Therapeuticsmentioning

confidence: 99%

Section: Development Of Peptides As Therapeuticsmentioning

confidence: 99%

Peptides as Therapeutic Agents for Dengue Virus

Chew

Poh

2017

Int. J. Med. Sci.

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“…The bias to certain self-antigens suggests that the immune system, too, might express an immunological homunculus -an internal image of key body molecules encoded by positive selection of antigen receptors to generate skewed repertoires of T cells and B cells [7][8][9]. Obviously, any self-antigen biases would have to enhance fitness; the autoimmunity expressed by repertoires of T cells and B cells in healthy individuals must be doing more good than harm [10][11][12][13][14].…”

Section: The Immunological Homunculusmentioning

confidence: 99%

Antigen-Microarray Profiling of Antibodies in SLE: A Personal View ofTranslation from Basic Science to the Clinic

Cohen¹

2016

Lupus Open Access

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In October of 2015, the startup company ImmunArray announced the launch of a microarray platform-the iChip ®-to profile repertoires of serum antibodies and autoantibodies. The first iChip ® product-the SLE-key ® RuleOut test-is designed to help the physician rule out a diagnosis of systemic lupus erythematosus (SLE) in suspected patients. The aim of this review is threefold: the first aim is to describe how basic observations and a philosophical notion led me to undertake the development of what has turned out to be a clinically useful aid in dealing with complex diseases; the second aim is to describe the role of a company in overcoming the technological and informatics challenges involved in translating basic research into patient welfare; the third aim is to discuss why SLE, like other complex medical problems, can be better managed using immune profiling. Basic scientist readers might learn here about the path to clinical application; clinician readers might learn here about the complicated origins of seemingly simple tests.

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Idiotype Network

Behn¹

2011

Encyclopedia of Life Sciences

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B‐lymphocytes have receptors, antibodies, with highly specific binding sites which bind to complementary structures. Receptors of a given cell have exactly one specific set of binding sites, the idiotype. Complementary structures can be found not only on antigen but also on antibodies of different idiotype or on T‐cell receptors. Thus a network of idiotypically interacting immune cells is formed, the idiotype network. The network influences the shaping of the B‐ and T‐cell repertoirs and may be relevant in the control of autoreactive clones. The therapeutic use of monoclonal antibodies against autoimmune diseases, cancer (in particular lymphoma) and a few other diseases relies on idiotypic interactions and is of rapidly growing importance. This strongly motivates further research to understand the systemic consequences of immunomanipulation. Key Concepts: An idiotope is a site on a B‐cell receptor that can bind to complementary structures; also on T‐cell receptors such sites exist. The collection of idiotopes on one receptor is called idiotype; all receptors of a given cell have the same specific idiotype. A huge diversity of idiotypes is generated by random somatic rearrangements of genes. B‐cells of a given idiotype are stimulated to proliferate if its receptors are cross‐linked by complementary structures; unstimulated cells die. Structures that bind to idiotopes can be found on antigen, not only on B or T cells of anti‐idiotype, but also on other cells or signalling molecules. Immune cells, functionally connected by idiotypic interactions, form the idiotype network which influences the shaping of the B‐ and T‐cell repertoir and may be relevant in the control of autoreactive clones. Therapeutic strategies using monoclonal antibodies rely on idiotypic interactions. New technologies make extensive studies of the repertoir of immune receptors feasable, which are necessary to better understand the network properties and systemic consequences of immunomanipulation. In many different fields the network paradigm has proved successful in describing complex systems, the recent progress in theoretical understanding should inspire further research on idiotype networks.

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Peptide therapy for Type I diabetes: the immunological homunculus and the rationale for vaccination

Cited by 48 publications

References 59 publications

Peptides as Therapeutic Agents for Dengue Virus

Peptides as Therapeutic Agents for Dengue Virus

Antigen-Microarray Profiling of Antibodies in SLE: A Personal View ofTranslation from Basic Science to the Clinic

Idiotype Network

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