Truncated MUC16 Targeting Mab AR 9.6 as Theranostic Agent for Cancer

Mechanism of Action:

  • Truncated MUC 16 induces oncogenic potential through EGF receptor and/or alpha 4 beta integrin.
  • 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:

  1. Target therapy for pancreatic cancer (Thomas et al 2021)
  2. Fluorescence antibody conjugate for intraoperative imaging (Olson et al 2020 and 2022)
  3. ImmunoPET of ovarian and pancreatic cancer (Sharma et al 2022)
  4. Radioimmunotherapy (Mack et al 2022)
  5. ADCC and CDC mediated tumor killing of pancreatic cancer (Rajesh 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:

  1. Novel method of targeting glycoproteins to treat cancer. Inventors: Hollingsworth M and Radhakrishnan P. US #10023652; China #ZL201480036588.4 (Issued July 2018)
  1. MUC16 monoclonal antibody and uses thereof. Inventors: Madiyalakan R, Hollingsworth M and Radhakrishnan P. Pending in US, Europe, China, and Canada (filed April 2019).


Mab AR9.6 publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.

Conference Presentations:

  1. Mack k, Mandleywala k, Samuels z, Brooks C, Radhakrishnan P, Hollingsworth M, Lewis J. Investigating the theranostic potential of a novel MUC16-targeted antibody for ovarian cancer. Nuclear Medicine and Biology 2022 108-109: S58
  2. 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.
  3. 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.