Opportunity Preview

MUC1 Cancer Antibody (Cancer Therapeutic)

Technology

Humanized antibody (hTAB004) targets pancreatic and triple negative breast cancers in preclinical models

Background

MUC1 is a transmembrane mucin glycoprotein found on the apical surface of most epithelial cells lining the ducts of major organs where roughly 85% of all cancers originate (breast, pancreas, stomach, colon, esophagus, lungs, etc.). A National Cancer Institute (NCI) sponsored pilot project prioritized MUC1 as a top target antigen from amongst 75 different cancer antigens in 2009. Tumor-associated MUC1 (tMUC1) differs from that expressed in normal cells, both in its biochemical features and its cellular distribution. Hence any moiety to target tMUC1 as a therapeutic agent should not target normal MUC1 to avoid toxicity.

tMUC1 targeting has the potential to lead to breakthroughs for the treatment of several cancers that are recognized as unmet needs including Pancreatic Cancer and Triple Negative Breast Cancer.

Technology Overview

A UNC Charlotte Irwin Belk Endowed Professor of Cancer Researcher, has developed a tumor specific antibody, TAB004, which specifically detects tMUC1. We have demonstrated in vivo targeting of breast and pancreatic ductal adenocarcinoma (PDAC) with TAB004 in immune competent transgenic mice that have human MUC1 in their entire normal epithelia. TAB004 localizes only on the cancer cells expressing tMUC1 but not on healthy tissue of these transgenic animals. TAB004 has also been shown to recognize pancreatic cancer stem cells, which are highly resistant to conventional chemotherapy and believed to be the primary reason for disease relapse. The antibody has also been fully humanized (hTAB004) to develop targeted immunotherapies. tMUC1 CAR T cells using the scFv of TAB004 showed tremendous promise in treatment of pancreatic and triple negative breast cancers in preclinical models.

Benefits

  • Can target most epithelial cancers without targeting healthy epithelial cells.
  • Antibody has been fully humanized.
  • Unlike several previous MUC1 antibodies, TAB004 only binds to surface bound antigen and does not bind to antigen in solution. Thus, TAB004 does not bind to tumor shed tMUC1 in circulation which has been a primary root cause of clinical trial failures with other MUC1 antibodies due to a sink effect that makes dosing to target the tumors difficult.

Applications

Our TAB004 antibody does not have a functional effect by itself but can be used to target tumors with cytotoxic agents or engineered cells using, amongst others, the following approaches:

  • TAB004 drug conjugate
  • Drug loaded nanoparticles functionalized with TAB004
  • CAR‑T cells (T-cells engineered with TAB004 scFv)-2nd and 3rd generation.
  • Natural Killer (NK) application

Additional TAB004 applications include:

  • Detection of circulating tumor cells (CTCs)
  • Immunohistochemistry

Opportunity

UNC Charlotte has been awarded over 12 issued patents globally for this technology. Exclusive license rights are available in multiple therapeutic areas.

Key Publications

  1. Curry JM, Thompson KJ, Rao SG, Besmer DM, Murphy AM, Grdzelishvili VZ, Ahrens WA, McKillop IH, Sindram D, Iannitti DA, Martinie JB, Mukherjee P. The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer. J Surg Oncol. 2013 Jun;107(7):713-22. doi: 10.1002/jso.23316. Epub 2013 Jan 17. PMID: 23335066; PMCID: PMC3880940. https://pubmed.ncbi.nlm.nih.gov/23335066/
  2. Moore LJ, Roy LD, Zhou R, Grover P, Wu ST, Curry JM, Dillon LM, Puri PM, Yazdanifar M, Puri R, Mukherjee P, Dréau D. Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors. Transl Oncol. 2016 Aug;9(4):295-305. doi: 10.1016/j.tranon.2016.05.001. PMID: 27567952; PMCID: PMC5006816. https://pubmed.ncbi.nlm.nih.gov/27567952/
  3. Dréau D, Moore LJ, Alvarez-Berrios MP, Tarannum M, Mukherjee P, Vivero-Escoto JL. Mucin-1-Antibody-Conjugated Mesoporous Silica Nanoparticles for Selective Breast Cancer Detection in a Mucin-1 Transgenic Murine Mouse Model. J Biomed Nanotechnol. 2016 Dec;12(12):2172-2184. doi: 10.1166/jbn.2016.2318. PMID: 28522938; PMCID: PMC5431076. https://pubmed.ncbi.nlm.nih.gov/28522938/
  4. Roy LD, Dillon LM, Zhou R, Moore LJ, Livasy C, El-Khoury JM, Puri R, Mukherjee P: A tumor specific antibody to aid breast cancer screening in women with dense breast tissue. Genes & Cancer 2017, 8(3-4):536-549 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489651/
  5. Salmon JSe: Phase II study of regorafenib (Reg) in patients with previously treated advanced pancreatic cancer (APC). JCO 2017, 35(15 suppl.). https://ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.e15751
  6. Wu S-t, Williams CD, Grover PA, Moore LJ, Mukherjee P (2018) Early detection of pancreatic cancer in mouse models using a novel antibody, TAB004. PLoS ONE 13(2): e0193260. https://doi.org/10.1371/journal.pone.0193260
  7. Zhou R, Yazdanifar M, Roy LD, Whilding LM, Gavrill A, Maher J, Mukherjee P. CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth. Frontiers in immunology, 2019 10: 1149 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543840/
  8. Yazdanifar M, Zhou R, Grover P, Williams C, Bose M, Moore LJ, Wu S-t, Chi R, Maher J, Dreau D. Overcoming Immunological Resistance Enhances the Efficacy of a Novel anti-tMUC1 CAR T Cell Treatment Against Pancreatic Ductal Adenocarcinoma. 2019, bioRxiv: 642934 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770201/
  9. Kelly VJ, Wu ST, Gottumukkala V, Coelho R, Palmer K, Nair S, Erick T, Puri R, Ilovich O, Mukherjee P: Preclinical evaluation of an (111)In/(225)Ac theranostic targeting transformed MUC1 for triple negative breast cancer. Theranostics 2020, 10(15):6946-6958 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295045/
  10. Tarannum M, Hossain MA, Holmes B, Yan S, Mukherjee P, Vivero-Escoto JL. Advanced Nanoengineering Approach for Target-Specific, Spatiotemporal, and Ratiometric Delivery of Gemcitabine-Cisplatin Combination for Improved Therapeutic Outcome in Pancreatic Cancer. Small. 2022 Jan;18(2):e2104449. doi: 10.1002/smll. https://pubmed.ncbi.nlm.nih.gov/34758094/
  11. Ru Zhou, Shu-ta Wu, Mahboubeh Yazdanifar, Chandra Williams, Alexa Sanders, Cory Brouwer, John Maher, and Pinku Mukherjee. Mucin-1–Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host, Journal of Immunotherapy ():10.1097/CJI. 0000000000000505, January 25, 2024. https://journals.lww.com/immunotherapy-journal/fulltext/9900/mucin_1_targeted_chimeric_antigen_receptor_t_cells.83.aspx