Press Release:

Bolstering the immune system’s power to fight cancer

June 14, 2021

University of Minnesota Medical School

As cancer progresses, a patient’s T-cells—which are critical for the immune system to function properly—become increasingly weakened. This can render immunotherapy, a treatment that helps one’s immune system fight cancer, ineffective.

Advancing a promising new treatment strategy.  Fortunately, University of Minnesota investigator Dr. Subbaya Subramanian is bringing new hope to cancer patients, particularly those with colorectal cancer, the second-leading cause of cancer-related deaths worldwide. He’s developing a new treatment approach for colorectal cancer patients that delivers immune-stimulating antigens along with anti-immunosupressant factors (i.e., mTEVs). The revolutionary method unlocks the normal T-cell costimulatory function to boost a patient's immune system.  Funding and guidance from CTSI in 2020 helped Dr. Subramanian advance his treatment closer to the point of helping people by supporting preclinical studies for evaluating its efficacy and antitumor immune response.  Forming a start-up, the effort continued building momentum, and in late 2020 Dr. Subramanian formed a start-up, EV Therapeutics, that will eventually license the technology and take over the development.  The treatment has the potential to transform the way cancer is treated, with more than five years of studies and data suggesting it may extend the survival outcomes or completely cure early-stage cancers.

As the second leading cause of cancer-related deaths world wide, colorectal cancer represents a high unmet medical need. CTSI support helped lead to a start-up—EV Therapeutics—that is developing a promising new treatment strategy for late-stage colorectal cancer.

Press Release:

Blocking immunosuppressive microRNAs in colorectal cancer cells proves effective in late-stage colorectal cancer treatment

Thu, April 29, 2021, 9:14 AM· 4 min read

Coloproctology News

University of Minnesota Medical School researchers have uncovered a new way to potentially target and treat late-stage colorectal cancer by identifying a novel mechanism by which colorectal cancer cells evade an anti-tumour immune response, which helped them develop an exosome-based therapeutic strategy to potentially treat the disease. "Late-stage colorectal cancer patients face enormous challenges with current treatment options. Most of the time, the patient's immune system cannot efficiently fight against tumors, even with the help of the FDA-approved cancer immunotherapies," said Dr Subree Subramanian, an associate professor in the U of M Medical School's Department of Surgery, and a senior author of the study. In partnership with Dr Xianda Zhao, a postdoctoral fellow in Subramanian's laboratory, the duo set out to investigate how colorectal cancer becomes resistant to available immunotherapies. The findings were published in the paper, 'Tumor secreted extracellular vesicles regulate T-cell costimulation and can be manipulated to induce tumoor specific T-cell responses', was published in Gastroenterology. Colorectal cancer cells secrete exosomes that carry immunosuppressive microRNAs  that actually prevent T cell and dendritic cell function because they block key proteins (CD28 and CD80) on these immune cell types, respectively. In the absence of these proteins, the T cells, which would normally kill the cancer cells, become ineffective and are eliminated from tumors, allowing tumors to grow.

By blocking these immunosuppressive microRNAs in cancer cells, the team observed an enhanced anti-tumor immune response and discovered that cancer cell-secreted exosomes also contain tumor-specific antigens that can stimulate the tumor-specific T cell response. The researchers tested tumor-secreted exosomes without immunosuppressive microRNAs, in combination with immune checkpoint inhibitors, as a novel combination therapy in preclinical models with advanced-stage colorectal cancer, which proved effective.

"Our studies indicate that disrupting specific immunosuppressive factors in tumor cells helps unleash the immune system to effectively control tumor growth and metastasis in preclinical models with late-stage colorectal cancer," said Subramanian, who is also a member of the Masonic Cancer Center. "Eliminating the immune suppressive effects of those exosomes is now the focus of a new treatment option for patients with this deadly disease."

The intellectual property behind the modified exosome technology has been protected with assistance from the U of M Technology Commercialization. EV Therapeutics is currently developing clinical-grade exosomes that can be tested in clinical trials for patients with colorectal cancer.