TNF based Bispecific ADC Development Service

Creative Biolabs is committed to providing high-quality bispecific antibody-drug conjugates (ADCs) services to support our clients’ projects. Through the method of covalent linkage, payloads can be efficiently attached to the antibody. Relying on the state-of-the-art facilities, our one-stop bispecific ADCs development will be meticulously monitored and controlled to ensure the high quality of final products.

Background

The Overview of TNF

The tumor necrosis factor (TNF) superfamily (TNFSF) and the TNF receptor (TNFR) superfamily (TNFRSF) form the corresponding ligand and receptor systems that are widely distributed in different tissues and cell types. Collectively they play critical roles in numerous aspects of mammalian biology, including embryonic development, innate and adaptive immunity, and maintenance of cellular homeostasis. Agents that manipulate the signaling of these receptors are being used or showing promise towards the treatment and prevention of many human diseases.

TNFSF members are generally homotrimeric type II transmembrane proteins, many of which can be shed from the cell surface to act as soluble signaling molecules. The defining feature of this family of extracellular ligands is the trimeric TNF homology domain (THD), comprising of three jelly roll protomers. Each protomer is formed by two β-sheets composed of strands A’AHCF and B’BGDE. These domains are exclusively located in the C-terminal region of the protein. The family can be divided into three groups (the conventional, the EF-disulfide containing, and the divergent), based on sequence and structural features in the THD.

Fig.1 Structures of TNFSF and TNFRSF members and complexes.¹

Antibodies-based Therapeutics Targeting TNF

There are several TNF antagonists are under development. All agents except are anti-TNF mAbs or fragments thereof, while etanercept is a genetically engineered fusion protein composed of a dimer of the extracellular portions of human TNFR2 fused to the Fc portion of human IgG1. Natural mAbs are derived from single B cells that clonally express copies of a unique heavy (H) chain and a unique light (L) chain that are covalently linked to form an antibody molecule of unique specificity. Being structurally identical to natural mAbs, engineered mAbs can are created by gene splicing and mutation procedures, mimicking natural gene rearrangement, and somatic mutation events in B cells.

Fig.2 Simplified diagrams of the molecular structures of 5 TNF antagonists.²

Our Service

TNF-based Bispecific ADCs Services

Bispecific antibodies (bsAb) targeting TNF and IL-23 are in preclinical development for the treatment of inflammatory bowel disease (IBD) and other autoimmune/inflammatory diseases. In a CD40-induced colitis model, a murine bsAb targeting IL-23 and TNF showed synergistic efficacy when compared to antibodies against TNF and IL-23 alone. A TNF x IL-23 bsAb would represent one of the first examples of a bsAb targeting two validated pathways with validated efficacy in IBD.

Creative Biolabs has devoted to the field of ADC for over a decade and established a series of comprehensive platforms to discover novel ADCs. We have constructed different epitope combinations for TNF-based bispecific ADCs development, including TNF x NGF, TNF x IL-1, TNF x IL-6R, TNF x IL-17A, and TNF x IL-23. With the extensive experience, abundant industry knowledge, and advanced technical skills, our scientists are fully confident in accomplishing even the most challenging project. If you are interested in our services, please contact us for more details.

Highlights

• Advanced bispecific ADC development platform: Creative Biolabs offers comprehensive services for constructing TNF-based bispecific ADCs, including combinations like TNF x IL-23 and TNF x IL-17A. Ensuring high efficacy in therapeutic development.
• Expertise in epitope combination design: With extensive experience, Creative Biolabs excels at creating diverse epitope combinations, such as TNF x NGF and TNF x IL-1, to enhance therapeutic outcomes. Tailored ADC solutions for complex diseases.
• Innovative TNF-targeting bispecific ADCs: Creative Biolabs is a leader in bispecific ADC production targeting TNF pathways, providing innovative therapies for autoimmune and inflammatory diseases. Revolutionizing treatments through targeted ADCs.
• Decades of experience in ADC innovation: With over ten years in the field, Creative Biolabs combines industry knowledge and technical skills to accomplish even the most challenging TNF-based ADC projects. Confidence in delivering exceptional results.
• Comprehensive expertise in ADC bio-conjugation: Creative Biolabs excels in covalently linking payloads to bispecific antibodies, ensuring stable and effective TNF-based ADCs. Optimizing ADC stability for therapeutic success.

FAQ

1. Q: What is the significance of TNF in bispecific ADC development?

   A: TNF plays a crucial role in immune regulation and inflammation, making it an ideal target for bispecific ADCs. Combining TNF with other immune-related targets, such as IL-23, enhances the therapeutic effect for diseases like IBD and autoimmune conditions.

2. Q: How does Creative Biolabs ensure the high quality of TNF-based bispecific ADCs?

   A: Creative Biolabs utilizes state-of-the-art facilities and rigorous quality control processes to develop TNF-based bispecific ADCs. Each stage of development is meticulously monitored to ensure the final product meets the highest standards.

3. Q: What types of bispecific ADCs targeting TNF can Creative Biolabs develop?

   A: Creative Biolabs develops a variety of TNF-based bispecific ADCs, including TNF x NGF, TNF x IL-1, TNF x IL-6R, TNF x IL-17A, and TNF x IL-23. Each combination is designed to target specific diseases with high therapeutic potential.

4. Q: How are payloads attached to antibodies in TNF-based bispecific ADCs?

   A: In TNF-based bispecific ADCs, payloads are covalently attached to antibodies using advanced bio-conjugation methods. This ensures stable linkage and efficient delivery of the cytotoxic agents to the targeted cells, maximizing therapeutic efficacy.

5. Q: Why is targeting TNF important in autoimmune and inflammatory disease therapies?

   A: TNF plays a key role in inflammatory processes. By inhibiting TNF in combination with other targets, bispecific ADCs can significantly reduce inflammation and improve outcomes in autoimmune and inflammatory diseases like rheumatoid arthritis and IBD.

6. Q: What are the potential applications of TNF-based bispecific ADCs in clinical settings?

   A: TNF-based bispecific ADCs are being explored for autoimmune diseases like IBD, rheumatoid arthritis, and inflammatory conditions. By combining TNF with other targets like IL-23, these therapies offer new treatment options with enhanced efficacy and reduced side effects.

Published Data

The BsNb targeting TNF-α and IL-23p19 was developed to enhance the treatment of inflammatory bowel disease (IBD) by blocking both TNF-α and IL-23 signaling pathways. This BsNb was further engineered into a tetravalent structure, BsNb-Fc, to improve its serum half-life and targeting capabilities. In mouse models of acute colitis induced by DSS and TNBS, BsNb-Fc outperformed current therapies like anti-TNF-α and anti-IL-23 (IFX & UST combination), significantly alleviating inflammation, reducing pro-inflammatory cytokine levels, and restoring intestinal integrity. BsNb-Fc's dual-targeting mechanism efficiently suppressed immune over-activation by inhibiting T-cell proliferation and inducing apoptosis in inflamed tissues, showing promise as a therapeutic option for patients unresponsive to TNF-α inhibitors.

Fig.3 BsNb-Fc treatment reduces the overexpression of pro-inflammatory cytokines triggered by DSS in colon tissue.³

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