Antibody-angiogenin ImmunoRNases Fusion Protein

Creative Biolabs provides customized antibody-angiogenin immunoRNases fusion protein development services for global clients by advanced technology platforms. Our professional scientists have extensive experience in antibody production, synthetic chemistry, as well as bio-conjugation andare committed to providing high-quality services to promote the development of innovative cancer treatments by using antibody-angiogenin immunoRNases fusion protein.

Angiogenin ImmunoRNases

An immunoRNase (IR) is an immuno-pro-toxin, as it can travel in the bloodstream, while magically selecting the cells targeted by the immune moiety. Once internalized, the RNase moiety will exert its RNA degrading activity, leading to the death of the targeted cell. By choosing a human RNase, and a human antibody fragment as immune moiety, an IR would be not only non-toxic but also non-immunogenic with greater specificity. Angiogenin (ANG), also known as RNase 5, is a member of the pancreatic RNase A superfamily. ANG is a plasma protein known for its angiogenic activities, especially in tumor growth.

Fig.1 Schematic representation of the main known functions of angiogenin. (Aparicio-Erriu, 2012)

Antibody-ANG ImmunoRNases Fusion Protein

As a result of steric hindrance, homodimeric RNases containing ANG have demonstrated improved tumor cytotoxicity over monomeric forms. For example, an anti-CD22 scFv diabody fused to two ANG molecules at the C-terminus via one (G₄S)₃ linker was constructed to target CD22⁺ B-cell non-Hodgkin lymphoma cells. The dimeric IR showed tumoricidal activity to CD22⁺ cells. CD30 ligand-specific ANG fusion proteins have previously demonstrated efficacy three-times greater than that of immunotoxins in lymphoma cells without the problem of immunogenicity. Besides, another CD30-specific IR was constructed with the ANG fused to the N- or C-terminal ends of the scFv, causing growth inhibition of CD30⁺ lymphoma cells with an IC₅₀ of 0.5-0.9 nM. In addition, the scFv-Fc-RNase construct was expressed in HEK 293T cells, yielding up to 4 mg/L soluble protein. This suggests that mammalian expression systems may be advantageous for the production of certain IRs.

Fig.2 Schematic setup of different CD30-specific antibody and immunoenzymes constructs generated. (Menzel, 2008)

The IR is a promising candidate for the immunotherapy of cancer because of its expected low immunogenicity and good production yields, as well as potent effector function upon target cell binding and internalization. Creative Biolabs is equipped with advanced research and manufacturing facilities and pleasured to help our clients design and prepare customized antibody-directed toxic enzyme fusion proteins using our featured services. With the novel technology platform and professional experiment services, Creative Biolabs gets ready to provide you with the best antibody services. Please feel free to contact us for more details.

References

1. Aparicio-Erriu, I. M.; Prehn, J. Molecular mechanisms in amyotrophic lateral sclerosis: the role of angiogenin, a secreted RNase. Frontiers in neuroscience. 2012, 6, 167.
2. Menzel, C.; et al. Human antibody RNase fusion protein targeting CD30+ lymphomas. Blood. 2008, 111(7), 3830-3837.

For Research Use Only. NOT FOR CLINICAL USE.