Recombinant Chimeric (human/mouse) monoclonal antibody expressed in CHO binding to Human EPHA3. KB004 is a first-in-class, monoclonal antibody targeting the EphA3 receptor tyrosine kinase. KB004 has the potential to attack tumors at their source by killing tumor stem cells, the tumor stromal cells that protect them, and the vasculature that feeds them. This unique activity provides the potential to generate durable responses by targeting the source of tumor cells. KB004 has been shown to be expressed in many tumor types, including hematologic malignancies and solid tumors.
Figure 1 EphA3 is expressed in stromal and vascular tissues of human tumors and mouse xenografts.
IHC of corresponding tumor xenografts to detect EphA3 (IIIA4 mAb, KB004). Scale bars, 50 mm. Insets show whole tumor, and magnified areas are indicated by boxes; scale bars, 1 mm.
Vail, M. E., Murone, C., Tan, A., Hii, L., Abebe, D., Janes, P. W., ... & Yarranton, G. (2014). Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. Cancer research, 74(16), 4470-4481.
Figure 2 ChIIIA4 disrupts integrity and function of tumor vessels.
Subcutaneous DU145 tumors, exposed on skin flaps, imaged by intravital multiphoton microscopy.
Vail, M. E., Murone, C., Tan, A., Hii, L., Abebe, D., Janes, P. W., ... & Yarranton, G. (2014). Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. Cancer research, 74(16), 4470-4481.
Figure 3 ChIIIA4 triggers cytoskeletal contraction, EphA3 phosphorylation, and apoptosis of tumor-derived EphA3⁺ MSCs.
α-PY-EphA3 immunoblot analysis of αEphA3 IPs from cells treated with combined chIIIA4/ephrin-A5. Phosphorylation in EphA3/HEK293T cells is shown for comparison.
Vail, M. E., Murone, C., Tan, A., Hii, L., Abebe, D., Janes, P. W., ... & Yarranton, G. (2014). Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. Cancer research, 74(16), 4470-4481.
Figure 4 Stromal and perivascular EphA3 expression in regenerating human endometrium.
Flow cytometry of endometrial stromal cell (eSC) samples testing co-expression of EphA3 and indicated cell surface markers; fractions of positively stained cells are indicated in each quadrant.
To, C., Farnsworth, R. H., Vail, M. E., Chheang, C., Gargett, C. E., Murone, C., ... & Lackmann, M. (2014). Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth. PloS one, 9(11), e112106.
Figure 5 EphA3 activation triggers phosphorylation, cell contraction, cell repulsion and cell-cell segregation of EphA3⁺ eMSCs.
Organoids formed by EphA3+ eMSC (red) and TEC (green) 3D co-cultures in Matrigel; nuclei stained with DAPI (blue). Treatments (.18 h) were: cross-linked (X-lkd) chimeric (ch)IIIA4 mAb.
To, C., Farnsworth, R. H., Vail, M. E., Chheang, C., Gargett, C. E., Murone, C., ... & Lackmann, M. (2014). Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth. PloS one, 9(11), e112106.
This is a product of Creative Biolabs' Hi-Affi™ recombinant antibody portfolio, which has several benefits including:
• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production
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