TNFRSF10B Specific Neutra™ Antibody Products

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TNFRSF10B (Tumor Necrosis Factor Receptor Superfamily Member 10b), alias TRAIL-R2, encompasses an intracellular domain facilitating apoptosis. Activation of this receptor ensues upon interaction with tumor necrosis factor-related apoptosis inducing ligand, instigating apoptotic signaling. Its involvement is noted in pathways such as procaspase-8 dimerization and gene expression regulation. Investigations employing FADD-deficient mice have underscored the indispensability of FADD, an adaptor protein harboring a death domain, in TNFRSF10B-mediated apoptosis. TNFRSF10B is implicated in conditions including laryngeal squamous cell carcinoma.

Its Gene ID: 8795, UniProtKB ID: O14763, and OMIM ID: 603612.

TNFRSF10B Related Pathway

The tumor necrosis factor (TNF)-linked apoptosis-inducing ligand receptor (TRAIL-R) family assumes a central role in regulating cell destiny and viability. TRAIL ligand binds to TRAIL-R1 or TRAIL-R2 (TNFRSF10B) and prompts the initiation of the extrinsic apoptotic route, then the recruitment of death domains, death-inducing signaling complex (DISC) assembly, activation of caspases, and consequent apoptosis. TRAIL receptors located on cell surfaces can bind with TRAIL from activated lymphocytes like NK cells, triggering apoptosis through caspase activation or the mitochondrial pathway by cytochrome c release. Additionally, TRAIL can activate the NF-κB pathway, promoting cell survival, while the ubiquitin-proteasome system aids in TRAIL-R degradation.

TNF-associated signaling pathway. Fig. 1 TNF-associated apoptosis signaling pathway.^{1, 3}

Anti-TNFRSF10B Antibodies

The therapeutic potential of TNFRSF10B antibodies has been investigated in Phase II clinical trials for non-small cell lung cancer (NSCLC), pancreatic cancer, ovarian cancer, colorectal cancer, and triple-negative breast cancer (TNBC). Moreover, several novel antibodies targeting TNFRSF10B are currently undergoing clinical evaluation, encompassing a spectrum of solid tumors and sarcomas.

Multiple TNFRSF10B-Targeting Antibodies in Cancer Therapy

Over the recent years, there has been growing interest in the development of therapies aimed at triggering apoptosis in cancer cells. This has led to the creation of numerous TRAIL analogs that target death receptor 5 (DR5/TNFRSF10B) for cancer treatment. Monoclonal antibodies (mAbs) against TNFRSF10B offer distinct advantages in tumor eradication. Their prolonged half-life and interaction capabilities via Fc domains with immune cell surface Fc receptors are particularly advantageous. Moreover, their high specificity enables them to function independently of decoy receptor expression within the tumor microenvironment.

Fig. 2 Schematic diagram of targeted therapeutic strategies against DR4 and DR5 in cancer.^{2, 3}

Advancing Cancer Therapy with TNFRSF10B Antibodies

Fully human agonistic mAbs with high affinity for human TRAIL receptor 2 (TRAIL-R2/TNFRSF10B) have been developed. TNFRSF10B is expressed on various tumor cell types and a limited number of normal cells. As a result, the interaction of TNFRSF10B antibodies triggers apoptosis in various cancer cell populations while exhibiting negligible impact on most healthy cells. Because of their specific lethality towards tumor cells, clinical trials are underway to explore the potential of recombinant human TRAIL and agonistic antibodies targeting TNFRSF10B for treating cancer. Agonistic TNFRSF10B antibodies may offer greater therapeutic potential than TRAIL owing to their prolonged in vivo half-life and lack of interaction with decoy TRAIL receptors. Furthermore, anti-TNFRSF10B mAbs have the potential to trigger Fc-mediated antibody effector mechanisms, including ADCC and CDC.

Creative Biolabs provides a broad selection of antibodies directed against TNFRSF10B, specifically designed for research purposes and the investigation of therapeutic approaches against a range of conditions, such as cancer. Additionally, our team of experts is available to deliver personalized functional antibodies (e.g. agonists, antagonists) against TNFRSF10B upon request.

REFERENCES

Sarhan, Dhifaf, Padraig D’Arcy, and Andreas Lundqvist. "Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system." International journal of molecular sciences 15.10 (2014): 18557-18573.
Dubuisson, Agathe, and Olivier Micheau. "Antibodies and derivatives targeting DR4 and DR5 for cancer therapy." Antibodies 6.4 (2017): 16.
Distributed under Open Access license CC BY 4.0, without modification.

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