Monoclonal Antibody Nomenclature

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List of syllables for the
nomenclature of monoclonal antibodies
prefix Effective range Organism of origin of the antibody Stem
old New meaning meaning
variable -anib- - Angiogenesis (inhibitor) -a- rat -mab
-ba (c) - -b (a) - bacteria -e- hamster
-ci (r) - -c (i) - blood circulation -i- Primates
-ung- -f (u) - Fungi -O- mouse
-ki (n) - -k (i) - Interleukin -u- humane
-les- - Lesion -xi- chimeric (human / foreign)
-li (m) - -l (i) - immune system -to- humanized
-mul- - Musculoskeletal system -xizu- * chimeric / humanized hybrid
-ne (u) (r) - -n (e) - * Nervous system -axo- Rat / mouse hybrid
-os- -so)- bone
-toxa- -tox (a) - toxin
-co (l) - -t (u) - Colon cancer
-go (t) - Testicular cancer
-go (v) - Ovarian cancer
-ma (r) - Breast cancer
-me (l) - Melanoma
-Per)- Prostate cancer
-tu (m) - various tumors
-vi (r) - -v (i) - virus
* in discussion since December 2009

The nomenclature for monoclonal antibodies is a convention for naming monoclonal antibodies using generic or non-proprietary names. An antibody is a protein produced in B cells and used by the human immune system and other vertebrates to identify specific foreign objects such as bacteria or viruses . As monoclonal antibodies are signified those who in identical cells - have been produced, and thus against a single - often artificially epitope align. Monoclonal antibodies are used especially in medicine in a wide range of applications .

This naming convention for monoclonal antibodies is used both in the international non-proprietary names (INN) of the World Health Organization and in the United States Adopted Names (USAN) for active substances. In general, word stems are used to distinguish between different classes of medicinal substances. All names of monoclonal antibodies end with the stem syllable -mab. In contrast to most of the other nomenclatures used for active substances, the monoclonal antibody nomenclature uses various preceding word parts ( morphemes ) depending on the structure or function.

Components

Structure ( ribbon model ) of an antibody. The four variable domains are on the very outside, see also top left and top right.

Stem

The word stem -mab is used both for monoclonal antibodies and for their fragments, as long as they contain at least one variable domain (the domain that binds the target). This applies, for example, to antigen binding fragments and single chain fragments. However, other parts of the antibody (such as Fc fragments) use different nomenclatures.

Origin organism of the antibodies

Organisms of origin of the antibodies: Images of mouse (top left), chimeric (top right), humanized (bottom left), chimeric / humanized (bottom center), and human (bottom right) monoclonal antibodies.
Parts of the antibody that occur in humans are shown in brown, parts of non-human origin in blue. The variable domains are shown at the top of each antibody; the complementarity determining regions within these domains are shown as triple loops

The stem of the word, which directly precedes the syllable -mab , suggests the animal origin of the monoclonal antibody. The first monoclonal antibodies were e.g. B. produced in mice (word stem -o-, compounded as -omab; usually the house mouse Mus musculus was used here) or by other non-human organisms. Neither INN nor USAN were ever consulted on the naming of antibodies derived from rats (syllable -a- ), hamsters ( -e- ), or primates ( -i- ).
These non-human monoclonal antibodies are recognized as foreign by the human immune system and can therefore be broken down quickly by the human body , they can trigger allergies , or both can apply. In order to mitigate these reactions of the human immune system, parts of the antibody have been replaced with humanized amino acid sequences , or pure human antibodies are produced technically . If the constant region is replaced by the human form, one speaks of chimeric monoclonal antibodies , identified by the syllable -xi-. Parts of the variable region can also be substituted for what is termed humanized ( -to- ); normally the entire sequence is replaced with the exception of the complementarity determining regions (CDRs), the three loops of the amino acid sequence at the very end of each variable domain, which are also decisive for binding to the target. Antibodies that are partly chimeric and partly humanized have the syllable -xizu-. However, these three syllables do not identify the foreign species. The human / mouse chimeric antibody basiliximab ends with -ximab as does the human / macaque antibody gomiliximab . Human antibodies use -u-.

Rat-mouse hybrids can be engineered to recognize the binding sites for two different antigens . These antigens, also known as tri-functional antibodies, carry the syllable -axo-.

Effective range

The syllable that precedes the original organism denotes the area of ​​activity of the monoclonal antibody. Examples of such areas of activity are tumors , organ systems such as the bloodstream , or pathogens such as bacteria or viruses . However, the range of action does not allow any conclusions to be drawn about the mode of action of the antibody in the body. Therapeutic , prophylactic and diagnostically used substances cannot be differentiated with this nomenclature.

In the naming convention originally developed, the individual syllables largely consisted of a consonant, followed by a vowel and again a consonant. The last letter could also be omitted to make pronunciation easier. Examples are -ci (r) - for the blood circulation, -li (m) - for the immune system and -ne (r) - for the nervous system. The last letter of the syllable is usually left out when the next syllable begins with a consonant (such as -zu- or -xi- ), but not all systems of effect are used in their short form. -mul-, for example, is never shortened to -mu- , as no chimeric or humanized antibodies that target the musculoskeletal system have received an INN to date . Combinations of syllables for mode of action and for the host organism end z. B. to -limumab (immune system, human) or -ciximab (blood circulation, chimeric, consonant r omitted).

New and shorter syllables for the scope were developed and adapted in 2009. Most consist of a consonant plus a vowel, which is omitted if the syllable for the host organism also begins with a vowel. For example, human antibodies that target the immune system are called -lumab instead of the old nomenclature -limumab. Some endings like -ciximab remain unchanged. The old system contained seven syllables for tumor targets - depending on the tumor type. However, because many antibodies respond to several tumor types, only the syllable -t (u) - is used in the new nomenclature .

prefix

The prefix has no special meaning, but it should be unique for each remedy and result in a melodious name. However, this also means that antibodies with the same target area and from the same host organism can only be differentiated by the prefix. Antibodies that respond to the exact same target, therefore, carry a different prefix (such as, for example, Ada limumab and Go limumab ). Both are TNF blockers , but differ in their chemical structure.

Additions to names

A second word can be added to the name of the active ingredient. There can be several reasons for this:

  • An antibody can be pegylated to slow the breakdown in the body and also to lower immunogenicity ; Addition: pegol as in alacizumab pegol.
  • A cytotoxic molecule can be linked to an anti-tumor antibody. Vedotin, for example, stands for monomethyl auristatin E , which itself is toxic but mainly attacks cancer cells when used in conjugates such as glembatumumab vedotin.
  • A chelator can also be added to bind radioisotopes . Pendetide, a derivative of diethylenetriaminepentaacetic acid , is z. B. used by capromab pendetide to chelate indium-111 . If the drug contains a radioisotope, the name of the isotope is placed in front of the name of the antibody. Indium ( 111 In) capromab pendetide is therefore the name for the above example, which contains indium-111.

history

Emil von Behring , one of the discoverers of antibodies

Emil von Behring and Kitasato Shibasaburō discovered in 1890 that diphtheria and tetanus in the bloodstream of animals were neutralized by substances they called anti-toxins . Behring received the first Nobel Prize in Physiology or Medicine in 1901 for this fundamental discovery. A year later, Paul Ehrlich coined the term antibody for these anti-toxins.

The principles for the production of monoclonal antibodies, also known as the hybridoma technique , were published in 1975 by Georges JF Köhler and César Milstein , who together with Niels Kaj Jerne received the 1984 Nobel Prize for Medicine . Muromonab-CD3 was the first monoclonal antibody to be approved for clinical use in humans in 1986.

The WHO introduced in 1950 a system of international non-proprietary name ( English International Nonproprietary Name : INN), where the first list with INN name three years later were published already. The syllable -mab for monoclonal antibodies was first proposed around 1990, with the system now used being developed between 1991 and 1993. As a result of the collaboration between WHO and the United States Adopted Names Council , the USAN names for antibodies have the same structure and are therefore largely identical to the INN names. By 2009, more than 170 monoclonal antibodies had been given names that followed this nomenclature. In October 2008, the WHO began to revise the nomenclature for monoclonal antibodies. In 2009, this led to adjustments to the nomenclature, especially in the designation of the area of ​​activity. In 2010 the first antibodies were named according to the new nomenclature.

Examples

New nomenclature

  • Olaratumab belongs to the group of antineoplastic drugs . The name is made up of the components olara-tu-mab , which suggests a human antibody with an area of ​​action against tumors .
  • Benralizumab is used to treat asthma , the name being composed of the syllables benra-li-zu-mab . This is derived from the fact that it is a humanized antibody that acts on the immune system.

Old nomenclature

  • Adalimumab is a monoclonal antibody that targets TNF-alpha . The name is made up of the syllables ada-lim-u-mab . This means that this human monoclonal antibody targets the immune system. According to the new nomenclature from 2009, the name would be adalumab .
  • Abciximab is a medication used to prevent platelets from clumping together . Broken down into the individual syllables ab-ci-xi-mab , it can be deduced that it is a chimeric monoclonal antibody whose area of ​​activity is the cardiovascular system . The name would also be the same according to the new nomenclature.
  • Trastuzumab , a monoclonal antibody used in the treatment of breast cancer , is made up of the syllables tras-tu-zu-mab . It is a humanized monoclonal antibody whose range of action extends to tumors. For this monoclonal antibody, too, the name would be identical according to the new nomenclature.

Different nomenclature

  • The monoclonal antibody muromonab-CD3 , first approved for clinical use in 1986, was named for monoclonal antibodies before this nomenclature was introduced. The name was composed of the parts of the word " mur ine mon oclonal a nti b ody (English for murine monoclonal antibody), targeting CD3 ".

See also

Individual evidence

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  26. Statement on a Nonproprietary name adopted by the USAN Council: Benralizumab (PDF) American Medical Association. Retrieved on April 28, 2014.  ( Page no longer available , search in web archives ) (Access only possible via login) @1@ 2Template: Dead Link / www.ama-assn.org
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