Highlights
- Biomarker assay based on CD74, designed to better indicate which patients may respond to immunotherapy
- Shows high sensitivity, fast turnaround and low experimental complexity
- Potential to make ICI treatments accessible for pMMR CRC patients, who are currently ineligible for immunotherapy
The opportunity
Anticancer therapy based on immune checkpoint blockade is one of the main treatments for colorectal cancer. Currently, Tumour Mutational Burden (TMB) as well as programmed cell death 1 (PD1) protein expression are used in the clinic as biomarkers of response to anti-PD1 immunotherapy. However, response is highly variable and approximately half of patients with hypermutated colorectal cancers show no durable benefit.
There is a need for new biomarkers to stratify patients who will respond to immunotherapy before initiating treatment.
We present a biomarker assay based on CD74, which is expressed at high levels not only in responsive hypermutated colorectal cancers, but also in a group of non-hypermutated colorectal cancers. This biomarker can help better indicate which patients may respond to immunotherapy.
The assay is both TMB and PD-L1 agnostic and is based on immunohistochemistry of a surface protein (CD74) expressed by cells in the tumour stroma. Thus, it shows high sensitivity, fast turnaround and low experimental complexity. Immunohistochemistry-based assays are routinely done in the pathology labs of any hospital with a variety of proteins with diagnostic or prognostic values.
Further, the assay has the potential to make ICIs (immune checkpoint inhibitors) accessible to CRC patients who are currently ineligible. Approximately 85% of CRCs show proficient DNA mismatch repair. Immunotherapy has shown efficacy in only dMMR CRC patients and it is currently not used in the treatment of pMMR CRCs, although several trials are ongoing. Measuring CD74 levels could predict whether someone with bowel cancer will respond to ICI, independent of which type of CRC they have. Crucially, this means that some people with the proficient subtype, who are currently ineligible for immunotherapy, might benefit from this treatment.
The data has been validated in both dMMR and pMMR bowel cancers from several international clinical trials demonstrating that patients who responded to ICI alone or in combination treatments had significantly higher levels of CD74 than those who did not respond. The work has been published on Cancer Cell in Jan 2025.
Developed by Professor Francesca Ciccarelli at The Francis Crick Institute.
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