Anti-Mouse DR5 (CD262) (Clone MD5-1) – PE

Mouse DR5-Ig fusion protein

This R-phycoerythrin (R-PE) conjugate is formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.4, 1% BSA and 0.09% sodium azide as a preservative.

Liquid

This R-phycoerythrin (R-PE) conjugate is stable when stored at 2-8°C. Do not freeze.

Research Use Only

2 – 8° C Wet Ice

Blue Laser (488 nm) and/or Green Laser (532 nm)/Yellow-Green Laser (561 nm)

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

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.