Rutherrin(R) Boosts Preclinical Immunotherapy Efficacy

Theralase® Technologies Inc., based in Toronto, has announced promising preclinical research results for its lead drug formulation, Rutherrin®. This clinical stage pharmaceutical company focuses on developing light and radiation-activated small molecules designed to target cancers, bacteria, and viruses. Their recent studies show that Rutherrin® can significantly enhance the efficacy of immunotherapy, a modern approach to cancer treatment.

Immunotherapy harnesses the immune system to detect and eliminate cancer cells. This type of treatment includes various forms such as checkpoint inhibitors, CAR T-cell therapy, cytokines, immunomodulators, cancer vaccines, monoclonal antibodies, and oncolytic viruses. Despite its potential, immunotherapy faces significant resistance challenges, leading to decreased treatment efficacy and increased adverse effects for patients.

Cancer cells evade the immune system by overexpressing checkpoint proteins on their surface, making them invisible to immune detection. Checkpoint inhibitors work by blocking these proteins, enabling the immune system to recognize and attack the cancer cells. However, multiple treatments are often required to overcome resistance, increasing the risk of severe side effects and treatment-related deaths.

Theralase®'s research indicates that Rutherrin® can enhance immunotherapy by directly killing cancer cells and reducing the expression of PD-L1 checkpoint proteins on cancer cells. This dual action lowers the number of checkpoint proteins that need to be blocked by immunotherapy, thereby improving treatment efficacy and safety. This approach results in a threefold strategy: Rutherrin® first targets and destroys cancer cells, then reduces PD-L1 protein expression, and finally allows immunotherapy drugs to effectively block the remaining PD-L1 proteins, enhancing immune system recognition and destruction of cancer cells.

In specific studies involving Non-Muscle Invasive Bladder Cancer (NMIBC) and Glioblastoma Multiforme (GBM), Rutherrin® significantly decreased PD-L1 expression on cancer cell surfaces, allowing immunotherapy drugs a better chance to block the remaining checkpoint proteins and enabling the immune system to identify and destroy the cancer cells.

Rutherrin®'s primary mechanism of action involves destroying NMIBC when activated by light and GBM and Non-Small Cell Lung Cancer (NSCLC) when activated by x-ray radiation. Its secondary mechanism involves unmasking cancer cells through dual immunogenic checkpoints, specifically CD47 and PD-L1 inhibition, enabling the immune system to detect and destroy these cells through a process known as Immunogenic Cell Death (ICD). ICD is characterized by the secretion of Damage-Associated Molecular Patterns (DAMPs), which signal the immune system to attack.

One DAMP, Calreticulin (CRT), functions as an "eat me" signal for the immune system. Research shows that combined Rutherrin® and x-ray radiation treatment significantly increases CRT surface expression, compared to radiation alone. This heightened CRT expression activates the immune system more effectively, enhancing the potential for cancer cell destruction locally and at metastatic sites.

Dr. Arkady Mandel, Chief Scientific Officer of Theralase®, emphasized the global health challenge posed by cancer and the promise of immunotherapy. He noted that cancer cells often develop resistance to immunotherapy, complicating treatment efforts. Rutherrin®'s ability to balance immune system "accelerators" and "brakes" could play a crucial role in enhancing immunotherapy's effectiveness while sparing healthy cells.

Roger DuMoulin-White, President and CEO of Theralase®, highlighted the goal of cancer therapies to eradicate the disease with minimal side effects. He expressed satisfaction with Rutherrin®'s potential to modulate the immune system by releasing its "brakes" and accelerating its attack on malignant cells, potentially establishing a new paradigm in cancer treatment.

Theralase® continues to focus on advancing the research and development of light and radiation-activated small molecules and their formulations to combat cancers, bacterial, and viral infections, with the dual objectives of efficacy and safety.