Anti-Mouse DR5 (CD262) (Clone MD5-1) – Purified in vivo PLATINUM™ Functional Grade

Mouse DR5-Ig fusion protein

This monoclonal antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Functional grade preclinical antibodies are manufactured in an animal free facility using in vitro cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s Purified Functional PLATINUM^TM antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at -80°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

Agonist,
FA,
FC,
IP,
WB

MD5-1 activity is directed against mouse DR5 (CD262).

DR5 is a member of the TNF-related apoptosis-inducing ligand (TRAIL) receptor family and acts as an agonist receptor that transmits death signals, it is also a transcriptional target of the known oncogene p53^1,2,3. Additionally, DR5 negatively regulates innate immune responses in dendritic cells⁴. DR5 is expressed in solid tumors and hematological malignancies in both mouse and humans¹, where it induces apoptosis via its functional cytoplasmic death domains². DR5 initiates apoptosis signals when its ligand, TRAIL, or an agonist monoclonal antibody, e.g., MD5-1, triggers a functional trimer configuration of its transmembrane helices and cytosolic domains¹. Apoptosis is induced in many types of transformed cells but not in normal cells⁵. Since TRAIL death receptors are elevated in a wide range of solid tumors, they are being investigated for the treatment of cancer^1,2.

MD5-1 was generated by immunizing an Armenian hamster with mouse DR5-Ig fusion protein⁵. Resulting splenocytes were fused with P3U1 mouse myeloma cells and screened for reactivity to mouse DR5-transfected BHK cells by flow cytometry. MD5-1 reacts with all TRAIL-sensitive tumor cells, including 4T1 mammary carcinoma and R331 renal carcinoma. MD5-1 acts as a death-inducing agonist when cross-linked by streptavidin, anti-hamster Ig monoclonal antibody, or FcR. Cytotoxic activity is completely abrogated by pan-caspase inhibitor z-VAD-fmk.

MD5-1 has been tested as a cancer therapy in mouse models of human cancer^5,6. MD5-1 inhibits TRAIL-sensitive tumor cell growth in vivo without toxicity and also primes tumor-specific T cells⁵. Additionally, MD5-1 in combination with anti-CTLA-4 retards tumor growth⁷.

DR5 (also known as CD262, TRAIL-Receptor 2, TNFRSF10b) is a plasma membrane bound receptor that also localizes to the cytoplasm and nucleus.

TRAIL (CD253); cytoplasmic domain interacts with TRADD and RIP

CD262

1. Piechocki MP, Wu GS, Jones RF, et al. Int J Cancer. 131(11):2562-2572. 2012.
2. Mert U, Sanlioglu AD. Cell Mol Life Sci. 74(2):245-255. 2017.
3. Willms A, Schupp H, Poelker M, et al. Cell Death Dis. 12(8):757. 2021.
4. Iyori M, Zhang T, Pantel H, et al. J Immunol. 187(6):3087-3095. 2011.
5. Takeda K, Yamaguchi N, Akiba H, et al. J Exp Med. 199(4):437-448. 2004.
6. Haynes NM, Hawkins ED, Li M, et al. J Immunol. 185(1):532-541. 2010.
7. Condamine T, Kumar V, Ramachandran IR, et al. J Clin Invest. 124(6):2626-2639. 2014.
8. Dufour F, Rattier T, Shirley S, et al. Cell Death Differ. 24(3):500-510. 2017.
9. Mondal T, Shivange GN, Tihagam RG, et al. EMBO Mol Med. 13(3):e12716. 2021.
10. Park C, Choi EO, Hwangbo H, et al. Nutr Res Pract. 16(3):330-343. 2022.