SUMMARY OF INVENTION

MSK investigators have developed three unique series of novel MUC16-targeting antibodies that efficiently inhibit tumor cell growth and invasion/metastasis. These antibody series address an important unmet medical need since, despite advances in tumor mutational analysis and immunotherapy, two thirds of ovarian cancer patients will recur and die of their disease.  New therapies are desperately needed.

MUC16 is present on the tissues of the female reproductive tract, and it is commonly over-expressed in tumors from these tissues, particularly ovarian cancer. Inhibiting tumor growth and invasion, these antibodies target the oncogenic domain retained on cancer cells following cleavage (MUC16^ECTO)—as opposed to the cleaved extracellular domain (CA-125) targeted by prior antibodies such as Oregovomab and DMUC5754A.  The low level of MUC16^ECTO in the circulation improves targeting over the cleaved tandem repeat CA125 target and its off-target effects in serosal sites. 

Additionally, this investigative team has successfully used ^MUC16ECTO-directed antibodies in different therapeutic formats, including Chimeric Antigen Receptor (CAR) T-cells, antibody drug conjugates (ADC), and bispecific T-cell engager cells (BiTEs). The MUC16^ECTO/CD3 BiTE increased overall survival in xenograft murine models of ovarian peritoneal carcinomatosis. The CAR T-cells were found to be safe in a Phase 1 trial for the treatment of ovarian cancer, demonstrating their potential use in different immunotherapy platforms to develop alternative therapeutic approaches.

ADVANTAGES

• While MUC16 is overexpressed in 70% - 80% of ovarian cancers, MUC16 levels are low in normal tissues, providing a large therapeutic window.
• MUC16 expression on the majority of ovarian cancer cells provides the opportunity to treat both minimal residual disease and advanced, measurable disease.
• CA125 can serve as  an already approved biomarker for patient selection for these novel MUC16ECTO therapies.
• Developed technologies provide potential for many integrated approaches, including direct antibody treatment, antibody conjugates, antibody + immune checkpoint combinations, adoptive T-cell therapy with Chimeric Antigen Receptors (CARs), and radioimmunotherapy with beta emitters such as 89Zr.

MARKET OPPORTUNITY

There are 20,000+ new cases of ovarian cancer in the U.S. each year, with limited therapeutic options. More than 12,000 women die from this disease annually, with five-year survival rates at only 46.5%. Other solid tumors with high MUC16^ECTO expression include uterine cancers, lobular breast cancer, and pancreatic cancers.

LEAD INVESTIGATOR

• David R.  Spriggs, MD, former Head, Division of Solid Tumor Oncology, MSK

RECENT PUBLICATIONS

• Rao et al. ACS Chem Biol. 2017 Aug 18; 12(8): 2085–2096 (PubMed link)
• Nemieboka et al: Nucl Med Biol. 2020 Jul-Aug; 86-87: 9–19. PMCID: PMC7311282 (PubMed link)
• Yeku et al. Front Immunol. 2021 Apr 14;12:663379 (PubMed link)

PATENTS

Comprehensive patent portfolio, including PCT/US2011/030025, PCT/US2016/022643, PCT/US2020/031886, and PCT/US2019/061503 (MSK internal code: SK1330, SK2014-012, SK2018-130, SK2018-131).

CONTACT INFORMATION:  Imke Ehlers, PhD, CLP, Director, Business Development & Licensing, MSK  [email protected]