Immune Checkpoint Therapy in Colorectal Cancer (CRC)

Colorectal Cancer (CRC) and Immune Checkpoint Therapy

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. It is estimated that about 50% of CRCs become metastatic during their evolution. Unfortunately, most patients cannot undergo resection of their metastases because of unresectable disease and/or comorbidities. Immune checkpoint inhibitors (ICIs) represent one of the major therapeutic breakthroughs in the history of medical oncology. In this context, metastatic colorectal cancer (mCRC) represents an intriguing entity, with a minority (4-5%) of tumors being highly sensitive to these compounds (i.e., CRC harboring microsatellite instability (MSI) and/or mismatch-repair deficiency (dMMR)), while a vast majority of immunologically cold tumors are refractory to immunotherapeutic strategies. It has been known for years that MSI/dMMR tumors are highly infiltrated by immune cells. These tumors are characterized by a high tumor mutational burden (TMB) with highly immunogenic neoantigens arising from frameshift mutations. Moreover, these tumors are associated with an upregulation of checkpoint inhibitors that exhaust intratumoral cytotoxic T lymphocytes and consequently protect MSI cancer cells from their hostile immune microenvironment.

Fig.1 Immune classification of colorectal cancer subtypes based on molecular pathway alteration. (Cohen, 2020)

Clinical Researches of Immune Checkpoint Therapy in CRC

Following the durable complete response of one patient with an MSI/dMMR mCRC treated with anti-PD1 ICI in a phase I study that included various types of unselected solid tumors, research and development of ICIs for CRC focused on MSI/dMMR mCRC. The impressive results of several phase II studies demonstrated that immune checkpoint inhibition is a breakthrough therapeutic strategy for dMMR/MSI mCRC. The efficacy of ICIs in MSI/dMMR mCRC is now well established, and trials are currently ongoing to assess ICI efficacy in first-line, adjuvant, or even neoadjuvant settings.

Services at Creative Biolabs

Having focused on immune checkpoint drug development for years, Creative Biolabs accumulated extensive experience from practice. With these valuable experience and strong foundations, we are confident in providing a series of quality-assured customer services for immune checkpoint-based CRC therapy development, including but not limited to:

• Immune Checkpoint Antibody Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Immune Checkpoint Assays
• Custom Immune Checkpoint Protein Development
• Immune Checkpoint Targeted Peptide Development
• Preclinical Research for Immune Checkpoint Drugs

If you are interested in any of our services, please do not hesitate to contact us for more information.

Reference

1. Cohen, R.; et al. Immune checkpoint inhibition in colorectal cancer: Microsatellite instability and beyond. Target Oncol. 2020, 15(1): 11-24.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.