Exosomal CEMIP and Anti-CEMIP Antibodies for Detection, Prevention and Treatment of Brain Metastasis

Background & Unmet Need

• Brain metastasis most commonly arises from lung and breast cancers, making up more than 50% of brain tumors in adults
• Despite its high lethality, brain metastasis is poorly prognosed and lacks effective therapies
• Current protocols for prognosis rely on brain scans of patients who already have symptoms, and it is difficult to predict who will develop brain metastasis
• Current treatment options include surgery, which is limited by tumor location, or radiation-based therapy, which is associated with cognitive decline. Moreover, brain metastasis has a high rate of recurrence
• Predicting brain metastases could be useful to put at-risk patients under closer surveillance and intervene before metastasis has occurred
• Unmet Need: Methods for prognosis, prevention, and treatment of brain metastasis

Technology Overview

• The Technology: A method to predict likelihood of brain metastasis based on the expression of cell migration-inducing and hyaluronan-binding protein (CEMIP) on tumor exosomes
• A therapeutic antibody targeting for prevention and treatment of cancer metastasis to the brain
• The Discovery: CEMIP is enriched in brain metastatic breast and lung tumor-derived exosomes
• Tumor-secreted factors, including exosomes, can reshape distant microenvironments, such as pre-metastatic niches, in order to drive organ-specific metastasis
• CEMIP remodels the brain microenvironment by inducing inflammation in the vascular niche, which promotes brain metastasis
• Depletion of CEMIP in tumors impairs brain metastasis, disrupting invasion and tumor cell association with the brain vasculature
• PoC Data: CEMIP was found to be enriched in the exosomes from brain metastatic cells
• Loss of CEMIP in brain-tropic breast cancer cells reduced the number of brain metastatic foci by 70%
• Patients with brain metastasis had significantly higher CEMIP expression, and metastases of the brain had higher CEMIP expression than other sites
• Patients with high levels of CEMIP expression had a shorter latency period for metastasis and significantly poorer prognoses
• Mice with brain-trophic metastatic breast cancer cells (BrT1) without CEMIP expression (KO) had 70% fewer metastatic foci and reduced metastatic burden in the brain 4 weeks post-injection compared to those with full CEMIP expression
• Antibodies to CEMIP have been generated in collaboration with the Tri-I TDI and tested for blocking capacity in vitro

Technology Applications

• Prognostic biomarker for risk of metastasis to the brain
• Method to non-invasively screen patients for primary and recurrent brain metastasis
• A biomarker for treatment selection for CEMIP-targeted therapies to prevent metastasis to the brain
• Prophylactic therapy for patients with high likelihood of metastasis to the brain
• Therapeutic treatment for patients with existing brain metastasis

Technology Advantages

• CEMIP may be detected and targetedat early stage, during pre-metastatic niche formation, which could allow for prevention of brain metastasis
• CEMIP may be detectable from patient plasma, and could serve a non-invasive biomarker for anti-CEMIP therapy

Figure 1: Mice intracardially injected with brain-trophic breast cancer metastatic cells (BrT1) with CEMIP knocked out had decreased brain metastatic tumor signal.