Neuro-endocrine prostate cancer (NEPC) accounts for about 20% of lethal metastatic castration-resistant prostate cancer (CRPC) cases. NEPC has the most aggressive biologic behavior of all prostate cancers and is associated with poor outcomes in patients. However, no effective treatment for NEPC exists because it exhibits distinct cell-surface expression profiles compared to other types of prostate cancer. Recently, CEACAM5 (known as CEA or CD66e) was identified as a specific surface protein marker for NEPC. However, developed anti-CEACAM5 antibodies for other cancers showed disappointing clinical results due to a lack of specificity and wrong epitope selection. In this regard, the development of a reliable and clinically applicable human monoclonal antibody with high specificity against CEACAM5 is in high demand.
Description
Since existing CEACAM5 antibodies lack specificity and have unclear epitopes, making them poor candidates for cancer therapy, Pitt inventors identified the first fully human monoclonal antibodies binding to membraneproximal domain of CEACAM5 from large phage display libraries. One antibody, with a well-defined epitope and affinity in the nanomolar range, exhibited specific binding of CEACAM5 without any cross-reactivity to either membrane-distal domains of CECAM5 or >5,800 human surface proteins, suggesting the highest specificity of any reported CEACAM5 antibodies. This antibody demonstrated promising cancer cell specific killing ability without offtarget toxicity in vitro, overcoming limitations of existing antibodies, and indicating its potential as a first-in-class drug for CEACAM5-positive cancers including NEPC.
Applications
• Treating NEPC and other cancers related to CEACAM5
Advantages
• First fully human monoclonal antibody against CEACAM5 (no murine sequences in CDRs and FRs)
• Target membrane-proximal region of CEACAM5, desired for immune cell engagers (CAR-T, CAR-NK, BiTE, BiKE)
• No cross-reactivity to other CEACAM family members
• No off-target binding to more than 5,800 human membrane proteins
• No other treatments exist for neuroendocrine prostate cancer
• Applicable to other CEACAM5-positive cancers
• Convertible to multiple immunotherapeutics
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20240166760A1
