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Synonyms: L01XC09 | Removab®
catumaxomab is an approved drug (EMA (2009))
Compound class: Antibody
Comment: Catumaxomab belongs to a novel generation of engineered monoclonal antibodies termed trifunctional (or Triomab®) antibodies [1,5-6].
Triomabs are hybrid antibodies that carry different antigen binding domains derived from rat IgG2b and mouse IgG2a monoclonals. One binding site (specified by the mouse IgG2a chain chain) is designed to interact with a specific tumour-associated antigen, in catumaxomab's case EpCAM. The other catumaxomab antigen binding site interacts with CD3e (specified by the rat IgG2b chain) on polyclonal T lymphocytes (effector cells). Finally, the intact Fc region of the Triomab® interacts with Fcγ receptors on accessory cells (monocytes/macrophages, natural killer cells and dendritic cells). This combination of interactions enables the formation of a tri-cell complex composed of tumour cells, T cells and accessory cells and promotes the synchronous activation of a variety of immune effector mechanisms that ultimately mediate an enhanced anti-tumour response.
1. Chelius D, Ruf P, Gruber P, Plöscher M, Liedtke R, Gansberger E, Hess J, Wasiliu M, Lindhofer H. (2010)
Structural and functional characterization of the trifunctional antibody catumaxomab.
MAbs, 2 (3): 309-19. [PMID:20418662]
2. Linke R, Klein A, Seimetz D. (2010)
Catumaxomab: clinical development and future directions.
MAbs, 2 (2): 129-36. [PMID:20190561]
3. Riesenberg R, Buchner A, Pohla H, Lindhofer H. (2001)
Lysis of prostate carcinoma cells by trifunctional bispecific antibodies (alpha EpCAM x alpha CD3).
J Histochem Cytochem, 49 (7): 911-7. [PMID:11410615]
4. Ruf P, Lindhofer H. (2001)
Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody.
Blood, 98 (8): 2526-34. [PMID:11588051]
5. Sebastian M, Passlick B, Friccius-Quecke H, Jäger M, Lindhofer H, Kanniess F, Wiewrodt R, Thiel E, Buhl R, Schmittel A. (2007)
Treatment of non-small cell lung cancer patients with the trifunctional monoclonal antibody catumaxomab (anti-EpCAM x anti-CD3): a phase I study.
Cancer Immunol Immunother, 56 (10): 1637-44. [PMID:17410361]
6. Shen J, Zhu Z. (2008)
Catumaxomab, a rat/murine hybrid trifunctional bispecific monoclonal antibody for the treatment of cancer.
Curr Opin Mol Ther, 10 (3): 273-84. [PMID:18535935]
7. Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B, Lindhofer H. (1999)
Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing.
J Immunol, 163 (3): 1246-52. [PMID:10415020]