Reprogramming the Canine Glioma Microenvironment with Tumor Vaccination plus Oral Losartan and Propranolol Induces...

Area of Science:

• Neuro-oncology
• Immunotherapy
• Cancer Stem Cell Research

Background:

• Malignant gliomas possess a highly immune-suppressive tumor microenvironment (TME).
• This immune suppression limits the efficacy of conventional therapies.
• Overcoming the TME's immune barrier is crucial for effective glioma treatment.

Purpose of the Study:

• To evaluate a novel therapeutic protocol combining myeloid cell targeted immunotherapy with tumor vaccination.
• To overcome the immune suppressive tumor microenvironment in malignant gliomas.
• To investigate the potential of this combined approach in a naturally occurring brain cancer model.

Main Methods:

• Utilized a canine glioma model for a prospective, open-label clinical trial.
• Administered oral losartan (monocyte migration inhibitor) and propranolol (myeloid-derived suppressor cell depleting agent) daily.
• Combined daily oral therapy with bi-weekly then monthly cancer stem cell (CSC) vaccination.
• Monitored tumor volume via MRI and correlated with immune responses, including anti-CSC antibody detection.

Main Results:

• An 80% overall clinical benefit rate was observed (2 partial regressions, 6 stable disease).
• Median overall survival was 351 days and median progression-free interval was 163 days.
• Dogs with detectable anti-CSC antibody responses showed significantly increased overall survival (500 days vs. 218 days, p=0.02).

Conclusions:

• Combining myeloid cell targeted oral immunotherapy with tumor vaccination can induce objective tumor responses.
• This therapeutic strategy shows promise for brain cancer patients, even without conventional treatments.
• The approach is readily implementable and warrants further investigation in clinical settings.