Monoclonal Antibody Therapy: What is in the name or clear description?
Curator: Demet Sag, PhD, CRA, GCP
What is in the name?
Nomenclature is important part of the scientific community so we can stay on the same page in all kinds of communications for clarity. Therefore, a defined nomenclature scheme for assigning generic, or nonproprietary, names to monoclonal antibody drugs is used by the World Health Organization’s International Nonproprietary Names (INN) and the United States Adopted Names (USAN). In general, word stems are used to identify classes of drugs, in most cases placed at the end of the word.
Knowing what Antibody relies on understanding of immune response system so that one can modify the cells, choose correct biomarkers from the primary pathways (like Notch, WNT etc), know signaling from outside to inside (like GPCRs, MAPKs, nuclear transcription receptors), personalized gene make up (genomics) and key gene regulation mechanisms. Thus, immunomodulation can be done for immunotherapies. The admiration of these cells generate the new era called biosensors.
- All monoclonal antibody names end with the stem -mab.
- Unlike most other pharmaceuticals, monoclonal antibody nomenclature uses different preceding word parts (morphemes) depending on antibody structure and function. These are officially called sub-stemsand sometimes erroneously infixes.
- This nomenclature is also used for fragments of monoclonal antibodies, such as antigen binding fragments and single-chain variable fragments.
The nomenclature has been updated. The main criteria is naming the origin, target, make up/type of antibody, ans of course suffix to show it is a monoclonal antibody.
Components
Substem for origin/source.
The substem preceding the -mab suffix denotes the animal from which the antibody is obtained.
The first monoclonal antibodies were produced
- in mice (substem -o-), yielding the ending -omab; usually Mus musculus, the house mouse),
- primates (-i-), yielding -imab;
- usually Macaca irus, the Crab-eating Macaque.
Need and RD:
There was a dis-advantage of using non-human Abs since they induce immune responses that are generating side effects, such as provoking allergy reactions, due to fast clearance from the body lost effectiveness etc.
As a result, new types of monoclonal antibodies were engineered developed to avoid negative impacts.
Mainly placing human origin sequences:
- Chimeric, the constant region is replaced with the human form so the substem used is -xi-., in which case it is called
- Humanized, Part of the variable regions, typically everything but the complementarity determining regions, may also be substituted, so substem used is -zu-.
- Partly chimeric and partly humanized antibodies use -xizu-.
*These three substems do not indicate the foreign species used for production.
Thus,
- the human/mouse chimeric antibody ba-s-il-i-ximab ends in -ximab
- the human/macaque antibody go-m-il-i-ximab ends in -ximab.
- Pure human antibodies use -u-.
Rat/mouse hybrid antibodies:
- They can be engineered with binding sites for two different antigens.
- These drugs, termed trifunctional antibodies, have the substem -axo–.
Substem for target
The substem preceding the source of the antibody refers to the medicine’s target.
Examples of targets are:
- tumors,
- organ systems like the circulatory system, or
- Infectious agents like bacteria or viruses.
However;
- The term targetdoes not imply what sort of action the antibody exerts.
- Therapeutic, prophylactic and diagnostic agents are not distinguished by this nomenclature.
In the naming scheme as originally developed, these substems mostly consist of a consonant, a vowel, then another consonant. For ease of pronunciation and to avoid awkwardness, the final consonant may be dropped if the following source substem begins with a consonant (such as -zu- or -xi-).
Examples of these include:
- -ci(r)- for the circulatory system,
- -li(m)-for the immune system (limstands for lymphocyte) and
- -ne(r)-or -neu(r)- for the nervous system.
This results in endings like –li-mu-mab (immune system, human) or –ci-ximab (circulatory system, chimeric, consonant r dropped).
In 2009, new and shorter target substems were introduced.
They mostly consist of a consonant, plus a vowel which is omitted if the source substem begins with a consonant.
For example, human antibodies targeting the immune system receive names ending in -lumab instead of the old -limumab. Some endings like -ciximab remain unchanged.
Prefix
The prefix carries no special meaning and should be unique for each medicine.
Additional words
A second word may be added if there is another substance attached or linked. If the drug contains a radioisotope, the name of the isotope precedes the name of the antibody.
Examples
New convention
- Olara-t-u-mab
- is an antineoplastic. Its name is composed of olara- + -t- + -u- + -mab.
- shows that the drug is a human monoclonal antibody acting against tumors.
- Benra-li-zu-mab
- a drug designed for the treatment of asthma,
- benra-+ -li- + -zu- + -mab, marking it as a humanized antibody acting on the immune system.
Recently, the bispecific antibodies, a novel class of therapeutic antibodies, have yielded promising results in clinical trials. In April 2009, the bispecific antibody catumaxomab was approved in the European Union.
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Selected FDA Approved Mab Drugs:
(John, Martin et al. 2005, Robert, Ann et al. 2006, Albert, Edvardas et al. 2012, Claro, Karen et al. 2012, Gideon, Nancy et al. 2013, Michael, Ke et al. 2013, Thomas, Albert et al. 2013, Hyon-Zu, Barry et al. 2014, Larkins, Scepura et al. 2015, Sandra, Ibilola et al. 2015, Sean, Gideon et al. 2015)
Albert, D., K. Edvardas, G. Joseph, C. Wei, S. Haleh, L. L. Hong, D. R. Mark, B. Satjit, W. Jian, G. Christine, B. Julie, B. B. Laurie, R. Atiqur, S. Rajeshwari, F. Ann and P. Richard (2012). “U.S. Food and Drug Administration Approval: Ruxolitinib for the Treatment of Patients with Intermediate and High-Risk Myelofibrosis.” Clinical Cancer Research: 3212-3217.
Claro, R. A. d., M. Karen, K. Virginia, B. Julie, K. Aakanksha, H. Bahru, O. Yanli, S. Haleh, L. Kyung, K. Kallappa, R. Mark, S. Marjorie, B. Francisco, C. Kathleen, C. Xiao Hong, B. Janice, A. Lara, K. Robert, K. Edvardas, F. Ann and P. Richard (2012). “U.S. Food and Drug Administration Approval Summary: Brentuximab Vedotin for the Treatment of Relapsed Hodgkin Lymphoma or Relapsed Systemic Anaplastic Large-Cell Lymphoma.” Clinical Cancer Research: 5845-5849.
Gideon, M. B., S. S. Nancy, C. Patricia, C. Somesh, T. Shenghui, S. Pengfei, L. Qi, R. Kimberly, M. P. Anne, T. Amy, E. K. Kathryn, G. Laurie, L. R. Barbara, C. W. Wendy, C. Bo, T. Colleen, H. Patricia, I. Amna, J. Robert and P. Richard (2013). “First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research: 4911-4916.
Hyon-Zu, L., W. M. Barry, E. K. Virginia, R. Stacey, D. Pedro, S. Haleh, G. Joseph, B. Julie, F. Jeffry, M. Nitin, K. Chia-Wen, N. Lei, S. Marjorie, T. Mate, C. K. Robert, K. Edvardas, J. Robert, T. F. Ann and P. Richard (2014). “U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia.” Clinical cancer research : an official journal of the American Association for Cancer Research: 3902-3907.
John, R. J., C. Martin, S. Rajeshwari, C. Yeh-Fong, M. W. Gene, D. John, G. Jogarao, B. Brian, B. Kimberly, L. John, H. Li Shan, C. Nallalerumal, Z. Paul and P. Richard (2005). “Approval Summary for Erlotinib for Treatment of Patients with Locally Advanced or Metastatic Non–Small Cell Lung Cancer after Failure of at Least One Prior Chemotherapy Regimen.” Clinical Cancer Research 11(18).
Larkins, E., B. Scepura, G. M. Blumenthal, E. Bloomquist, S. Tang, M. Biable, P. Kluetz, P. Keegan and R. Pazdur (2015). “U.S. Food and Drug Administration Approval Summary: Ramucirumab for the Treatment of Metastatic Non-Small Cell Lung Cancer Following Disease Progression On or After Platinum-Based Chemotherapy.” The oncologist.
Michael, A., L. Ke, J. Xiaoping, H. Kun, W. Jian, Z. Hong, K. Dubravka, P. Todd, D. Zedong, R. Anne Marie, M. Sarah, K. Patricia and P. Richard (2013). “U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.” Clinical cancer research : an official journal of the American Association for Cancer Research: 2289-2293.
Robert, C. K., T. F. Ann, S. Rajeshwari and P. Richard (2006). “United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy.” Clinical cancer research : an official journal of the American Association for Cancer Research: 2955-2960.
Sandra, J. C., F.-A. Ibilola, J. L. Steven, Z. Lillian, J. Runyan, L. Hongshan, Z. Liang, Z. Hong, Z. Hui, C. Huanyu, H. Kun, D. Michele, N. Rachel, K. Sarah, K. Sachia, H. Whitney, K. Patricia and P. Richard (2015). “FDA Approval Summary: Ramucirumab for Gastric Cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research: 3372-3376.
Sean, K., M. B. Gideon, Z. Lijun, T. Shenghui, B. Margaret, F. Emily, H. Whitney, L. Ruby, S. Pengfei, P. Yuzhuo, L. Qi, Z. Ping, Z. Hong, L. Donghao, T. Zhe, H. Ali Al, B. Karen, K. Patricia, J. Robert and P. Richard (2015). “FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer.” Clinical cancer research : an official journal of the American Association for Cancer Research: 2436-2439.
Thomas, M. H., D. Albert, K. Edvardas, C. K. Robert, M. K. Kallappa, D. R. Mark, H. Bahru, B. Julie, D. B. Jeffrey, H. Jessica, R. P. Todd, J. Josephine, A. William, M. Houda, B. Janice, D. Angelica, S. Rajeshwari, T. F. Ann and P. Richard (2013). “U.S. Food and Drug Administration Approval: Carfilzomib for the Treatment of Multiple Myeloma.” Clinical Cancer Research: 4559-4563.
Further Reading:
Waldmann, Thomas A. (2003). “Immunotherapy: past, present and future”. Nature Medicine 9 (3): 269–277. doi:10.1038/nm0303-269. PMID 12612576.
Sharma, Pamanee; Allison, James P. (April 3, 2015). “The future of immune checkpoint therapy”. Science. doi:10.1126/science.aaa8172. Retrieved June 2015.
Gene Garrard Olinger, Jr., James Pettitt, Do Kim, Cara Working, Ognian Bohorov, Barry Bratcher, Ernie Hiatt, Steven D. Hume, Ashley K. Johnson, Josh Morton, Michael Pauly, Kevin J. Whaley, Calli M. Lear, Julia E. Biggins, Corinne Scully, Lisa Hensley, and Larry Zeitlin (2012). “Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques”. PNAS 109 (44): 18030–5.doi:10.1073/pnas.1213709109. PMC 3497800. PMID 23071322.
Janeway, Charles; Paul Travers; Mark Walport; Mark Shlomchik (2001).Immunobiology; Fifth Edition. New York and London: Garland Science. ISBN 0-8153-4101-6.
Janeway CA, Jr.; et al. (2005). Immunobiology. (6th ed.). Garland Science. ISBN 0-443-07310-4.
Modified from Carter P (November 2001). “Improving the efficacy of antibody-based cancer therapies”. Nat. Rev. Cancer 1 (2): 118–29. doi:10.1038/35101072.PMID 11905803.
Prof FC Breedveld (2000). “Therapeutic monoclonal antibodies”. Lancet.doi:10.1016/S0140-6736(00)01034-5.
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Nadler LM, Stashenko P, Hardy R, et al. (September 1980). “Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen”.Cancer Res. 40 (9): 3147–54. PMID 7427932.
Stern M, Herrmann R (April 2005). “Overview of monoclonal antibodies in cancer therapy: present and promise”. Crit. Rev. Oncol. Hematol. 54 (1): 11–29.doi:10.1016/j.critrevonc.2004.10.011. PMID 15780905.
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Chames, Patrick; Baty, Daniel (2009). “Bispecific antibodies for cancer therapy: The light at the end of the tunnel?”. MAbs 1 (6): 539–547. doi:10.4161/mabs.1.6.10015.PMC 2791310. PMID 20073127.
Linke, Rolf; Klein, Anke; Seimetz, Diane (2010). “Catumaxomab: Clinical development and future directions”. MAbs 2 (2): 129–136. doi:10.4161/mabs.2.2.11221.
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