Mimotope

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Mimotopes (from English mimic , imitate and epitope ) are artificially produced peptides or small proteins which imitate the structural recognition features of an antigen , the so-called epitopes. Like their role models, mimotopes are recognized by specific antibodies and, depending on the modification, can trigger a defined immune response . The immune system activated by mimotopes recognizes both the triggering mimotope and the antigen serving as a model in a cross reaction. Mimotopes are therefore particularly suitable for generating an immune response against unknown antigens or antigens without sufficient immunogenicity of their own . Mimotopes represent a potential option for cancer immunotherapy , among other things .

properties

Mimotopes are peptides with a chain length of 6 to 20 amino acids . This chain length is the minimum size of a peptide that is necessary for a humoral and cellular immune response. Due to their low molecular mass , mimotopes have a high resistance to heat and cold. In addition, due to their simplicity, they can be produced in large quantities using conventional methods of peptide chemistry.

Manufacturing

Mimotopes can be obtained with the aid of display techniques, such as phage display , using an antibody that recognizes the target antigen. In this biotechnological method, large molecular libraries encoded by bacteriophages , which usually contain several billion different encoded peptides, are searched for antibody-binding peptides. The mimotopes obtained in this way can be further modified. For example, with the help of multimerization, their effectiveness can often be increased and the immune reaction can be controlled in a targeted manner through conjugation. Mimotopes are listed in the MimoDB database .

application

So far, mimotopes have only been used experimentally. In addition, medical use for a variety of uses including the treatment of allergies , infectious diseases and cancer is discussed. Mimotope-based vaccines are in preclinical development .

Of particular interest is the possibility of generating an immune reaction against antigens without sufficient intrinsic immunogenicity with the aid of mimotopes. Characteristic polysaccharide and lipid epitopes on antigens of numerous pathogens and tumor cells are recognized by the immune system, but do not lead to a T-cell- mediated immune reaction. Immune reactions against these antigens are limited and do not lead to the formation of memory cells and affinity-matured antibodies.

Since only one antibody has to be available to produce a mimotope, but no information about the antigen to be recognized is required, these peptides are also suitable for the production of potential immunotherapeutic agents against unknown target structures. Mimotopes are also suitable as potential vaccines for antigens which, due to their molecular size, for example, cannot be produced in an amount sufficient for direct active immunization.

Individual evidence

  1. ↑ Knittelfelder R, Riemer AB, Jensen-Jarolim E: Mimotope vaccination - from allergy to cancer . In: Expert Opin Biol Ther . 9, No. 4, April 2009, pp. 493-506. doi : 10.1517 / 14712590902870386 . PMID 19344285 .
  2. ↑ Pirofski LA: Polysaccharides, mimotopes and vaccines for fungal and encapsulated pathogens . In: Trends Microbiol. . 9, No. 9, September 2001, pp. 445-51. PMID 11553457 .
  3. ↑ Popkov M, Sidrac-Ghali S, Alakhov V, Mandeville R: Epitope -specific antibody response to HT-1080 fibrosarcoma cells by mimotope immunization . In: Clin. Cancer Res . 6, No. 9, September 2000, pp. 3629-3635. PMID 10999755 .
  4. ↑ Wagner S, Hafner C, Allwardt D, et al. : Vaccination with a human high molecular weight melanoma-associated antigen mimotope induces a humoral response inhibiting melanoma cell growth in vitro . In: J. Immunol. . 174, No. 2, January 2005, pp. 976-82. PMID 15634921 .

literature

  • Monzavi-Karbassi B, Cunto-Amesty G, Luo P, Kieber-Emmons T: Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery . In: Trends Biotechnol . . 20, No. 5, May 2002, pp. 207-214. PMID 11943376 .
  • Riemer AB, Jensen-Jarolim E: Mimotope vaccines: epitope mimics induce anti-cancer antibodies . In: Immunol. Lett. . 113, No. 1, October 2007, pp. 1-5. doi : 10.1016 / j.imlet.2007.07.008 . PMID 17825923 . PMC 2999752 (free full text).