MUC 16 also binds to mesothelin leading to metastasis.
Structural characterization of Mab AR 9.6 in complex with MUC16 revealed a non-linear epitope influenced by glycosylation.
MAb AR 9.6 blocks oncogenic activities and tumor growth.
Clinical Applications:
Target therapy for pancreatic cancer (Thomas et al 2021)
Fluorescence antibody conjugate for intraoperative imaging (Olson et al 2020 and 2022)
ImmunoPET of ovarian and pancreatic cancer (Sharma et al 2022)
Radioimmunotherapy (Mack et al 2022)
Developmental stage
Preclinical development underway for pancreatic cancer.
Stable CHO cells expressing humanized Mab AR 9.6 have been developed.
Patent status:
Novel method of targeting glycoproteins to treat cancer. Inventors: Hollingsworth M and Radhakrishnan P. US #10023652; China #ZL201480036588.4 (Issued July 2018)
MUC16 monoclonal antibody and uses thereof. Inventors: Madiyalakan R, Hollingsworth M and Radhakrishnan P. US# 11,773,183. Pending in Europe, China, and Canada.
Mab AR9.6 publications
Olson MT, Aguilar EN, Brooks CL, Isder CC, Muilenburg KM, Talmon GA, Ly QP, Carlson MA, Hollingsworth MA, Mohs AM. Preclinical Evaluation of a Humanized, Near-Infrared Fluorescent Antibody for Fluorescence-Guided Surgery of MUC16-Expressing Pancreatic Cancer. Mol Pharm. 2022 Oct 3;19(10):3586-3599. PMID: 35640060.
Rajesh C, Sagar S, Rathinavel AK, Chemparathy DT, Peng XL, Yeh JJ, Hollingsworth MA, Radhakrishnan P. Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling. Int J Mol Sci. 2022 May 13;23(10):5459. PMID: 35628269.
White B, Patterson M, Karnwal S, Brooks CL. Crystal structure of a human MUC16 SEA domain reveals insight into the nature of the CA125 tumor marker. Proteins. 2022 May;90(5):1210-1218. PMID: 35037700.
Sharma SK, Mack KN, Piersigilli A, Pourat J, Edwards KJ, Keinänen O, Jiao MS, Zhao H, White B, Brooks CL, de Stanchina E, Madiyalakan MR, Hollingsworth MA, Radhakrishnan P, Lewis JS, Zeglis BM. ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody. Clin Cancer Res. 2022 Mar 1;28(5):948-959. PMID: 34907079.
Thomas D, Sagar S, Liu X, Lee HR, Grunkemeyer JA, Grandgenett PM, Caffrey T, O’Connell KA, Swanson B, Marcos-Silva L, Steentoft C, Wandall HH, Maurer HC, Peng XL, Yeh JJ, Qiu F, Yu F, Madiyalakan R, Olive KP, Mandel U, Clausen H, Hollingsworth MA, Radhakrishnan P. Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer. Mol Ther. 2021 Apr 7;29(4):1557-1571. PMID: 33359791.
Olson MT, Wojtynek NE, Talmon GA, Caffrey TC, Radhakrishnan P, Ly QP, Hollingsworth MA, Mohs AM. Development of a MUC16-Targeted Near-Infrared Fluorescent Antibody Conjugate for Intraoperative Imaging of Pancreatic Cancer. Mol Cancer Ther. 2020 Aug;19(8):1670-1681. PMID: 32404409.
Aguilar EN, Sagar S, Murray BR, Rajesh C, Lei EK, Michaud SA, Goodlett DR, Caffrey TC, Grandgenett PM, Swanson B, Brooks TM, Black AR, van Faassen H, Hussack G, Henry KA, Hollingsworth MA, Brooks CL, Radhakrishnan P. Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6. Mol Cancer Ther. 2024 Feb 23. doi: 10.1158/1535-7163.MCT-23-0868. Epub ahead of print. PMID: 38394685.
Kyeara Mack, Zachary Samuels, Lukas Carter Tara Viray, Komal Mandeleywala, Cory Brooks, Michael Hollingsworth, Prakash Radhakrishnan, and Jason Lewis. Interrogating the Theranostic Capacity of MUC16-Targeted Antibody for Ovarian Cancer. Journal of Nuclear Medicine 2024 May 2024
Conference Presentations:
Rajesh C, Sagar s, Brooks C, Hollingsworth M, Radhakrishnan P. Immunotherapeutic potential of the humanized anti-MUC16 antibody AR9.6 against PDAC. J Immunother. Cancer 2022 10 (suppl 2) A181.
2. Brooks c, Auguilar EN, White B, van Faassen H, Michud, SA, Goodlet D, Brooks TM, Hussack G, Henry KA, Radhakrishnan P, Structure of MUC16 specific antibody in complex with the cancer antigen 125. Keystone conference 2023.
Brooks, C.L., White, B., Aguilar, E., van Hassen, F., Michaud, S.A., Goodlett, D., Brooks, T.M., Hussack, G., Henry, K., Radhakrishnan P. Characterization of AR9.6: A novel MUC16 Specific mAb for Pancreatic Cancer. Festival of Biologics. San Diego, CA. Mar. 19-21, 2023.
Brooks, C.L., White, B., Aguilar, E., van Hassen, F., Michaud, S.A., Goodlett, D., Brooks, T.M., Hussack, G., Henry, K., Radhakrishnan P., Structure of a Therapeutic Antibody in Complex with MUC16 Reveals a Conformational Epitope Influenced by Antigen Glycosylation. April 2 – 5, 2022, Experimental Biology. Philadelphia, PA
We use cookies to analyze website traffic and optimize your website experience. By accepting our use of cookies, your data will be aggregated with all other user data.