Developing Novel First-in-Class Therapeutics for Colorectal Cancer

Summary

• Colorectal cancer (CRC) is major cause of morbidity and mortality in the United States
• Breakthrough immunotherapies, such as checkpoint inhibitors can induce rapid and sustained clinical outcomes
• However, therapy resistance is a major barrier to treatment and novel strategies to combat CRC and improve existing therapies are urgently needed
• Group 3 innate lymphoid cells (ILC3s) are tissue resident cells that regulate immunity, inflammation, and tissue homeostasis
• Dr. Sonnenberg, recognized leader in intestinal disorders, is at the forefront of interrogating the function, regulation and therapeutic potential of tissue resident ILC3s, for mediating chronic intestinal inflammation
• The Sonnenberg lab has identified that ILC3s are novel antigen presenting cells that induce tolerance and limits microbiota-specific effector CD4+ T cells

Technical Overview

The Sonnenberg lab has defined 3 critical aims to better understand the role of ILC3s in the tumor microenvironment of CRC (see figure):

• Evaluate whether ILC3s can be utilized as a cell-based therapy to limit tumor progression in a mouse model CRC driven by KRAS and/or APC mutations
• Evaluate whether the ILC3-to-ILC1 plasticity be modeled in vitro to identify new targets to block this pathway of dysregulation in CRC
• Evaluate scRNA-sequencing of innate and adaptive lymphocytes to better define mechanisms or targets driving inherent immune dysregulation in CRC

Through this work, Dr. Sonnenberg aims to comprehensively define the potential to harness ILC3s as a therapeutic target in CRC, and to identify novel pathways that are causing ILC3 dysfunction in cancer

Market Opportunity

• Colorectal cancer has the second highest cost of any cancer in the United States
• Studying the role of ILC3s in CRC will enable a comprehensive understanding of the dynamic nature of the tumor microenvironment
• Targeting ILC3s may offer a new avenue to effectively and sustainably treat therapy resistant CRC

Partnering Opportunity

Weill Cornell Medicine is seeking a strong industrial partner with a market leading franchise in the oncology space to explore the potential for ILC3s to be harnessed as a novel therapeutic strategy to combat CRC

Figure 1: Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer.