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Triomab Generation Service

Creative Biolabs is an undisputed global leader in the rapidly emerging market of bispecific antibodies (BsAbs). Based on the well-established BsAbs production platform, we offer a full range of high quality BsAbs, including the trifunctional hybrid antibodies (Triomab).

Triomab Antibodies

Triomab antibodies are comprised of two different full-size IgG-like half antibodies from two different species, such as rat IgG2b and mouse IgG2a isotypes. Most of reported Triomabs are generated by rat/mouse hybrid-hybridomas. The resulting BsAbs have correct species-restricted H/L chain pairing which reduces the mismatch variants. Triomab can bind two distinct antigenic structures, for example, tumor-associated antigens and the CD3 molecule on T-cells, as well as binding to Fcγ-receptors by the Fc-region on accessory cells. Triomab molecules mediate generation of tri-cell complexes, and in this manner typical antibody therapy, such as passive immunization, enable to be transformed into active in situ immunization. Primarily, Triomab-based cancer treatment concept contains directed cytotoxic activity of T cells, participation of accessory cells and their costimulatory signaling, as well as Th1-type cytokine induced pro-inflammatory responses. Therefore, use of Triomab antibodies may immunize patients specifically against their own primary tumors, hence protecting them from future relapses.

Schematic diagram of the mode of action of Triomabs.

Figure 1. Schematic diagram of the mode of action of Triomabs. The Triomab configuration enables the production of a tri-cellular complex comprising three cell types: T cells, tumor cells and Fc receptor-expressing accessory cells. (Grandjenette, C., 2015)

Approved and Clinical Stage of Triomabs

Currently, there are two well-known Triomabs, named Catumaxomab and Ertumaxomab. Catumaxomab, the first approved Triomab in patients, is an anti-EpCAM-anti-CD3 Triomab. A phase-I trial of a single intravenous (i.v.) dose of catumaxomab in patients with non-small cell lung cancer (NSCLC), built a maximum tolerated dose and displayed favorable survival in many patients with advanced-stage disease surviving past 26 months. Besides, a number of other studies have assessed i.p. administration of catumaxomab in patients with malignant ascites caused by a variety of EpCAM positive tumors. Ertumaxomab is an anti-Her2-anti-CD3 Triomab. This Triomab was exhibited to induce effective immune mediated cytotoxicity against Her2 expressing tumor cell lines in vitro, and to strongly lyse low Her2 expressing target cells where trastuzumab was absolutely ineffective.

Development in BsAbs engineering has marked a novel era of antibody based cancer treatment and has led to an array of constructs shown to be powerful in inducing target cell killing by engaged effector cells. With our well-established Triomab generation platform, the experienced scientists here at Creative Biolabs are dedicated to help you develop unique Triomabs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Grandjenette, C.; et al. Bispecific antibodies: an innovative arsenal to hunt, grab and destroy cancer cells. Current pharmaceutical biotechnology. 2015, 16(8), 670-683.
2. Lameris, R.; et al. Bispecific antibody platforms for cancer immunotherapy. Critical reviews in oncology/hematology. 2014, 92(3), 153-165.
3. Chelius, D.; et al. Structural and functional characterization of the trifunctional antibody catumaxomab. Mabs. 2010, 2(3): 309-319.

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