On June 18, 2024 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated small molecules and their formulations, intended for the safe and effective destruction of various cancers, bacteria and viruses, reported that in preclinical research, it’s lead drug formulation, Rutherrin, has demonstrated an ability to increase the efficacy of immunotherapy (Press release, Theralase, JUN 18, 2024, View Source [SID1234644440]).
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Immunotherapy, the latest technology in the war on cancer, can come in various forms; including: checkpoint inhibitors, Chimeric Antigen Receptor ("CAR") T-Cell therapy, cytokines, immunomodulators, cancer vaccines, monoclonal antibodies and oncolytic viruses, but the fundamental Mechanism Of Action ("MOA") of all of these immunogenic drugs is to stimulate the immune system to destroy cancer cells.
Cancer cells hide from the immune system by overexpressing proteins on their cellular surface, known as checkpoint proteins, that prevent the immune system from recognizing and subsequently destroying them. They thus remain incognito to the one failsafe that can protect the human body, the immune system.
The MOA of checkpoint inhibitors is to block the PD-L1 (checkpoint protein) on the cancer cell surface, allowing the immune system to detect and destroy the cancer cell; however, resistance to immunotherapy remains one of the major challenges in this form of treatment. In an attempt to overcome this resistance, multiple immunotherapy treatments are delivered to the patient, which may ultimately lead to a diminishing return in efficacy and a corresponding increase in patient serious adverse events and even treatment-related death.
Theralase’s latest research demonstrates that Rutherrin enhances the MOA of immunotherapy by not only killing cancer cells directly, but also significantly reducing the amount of PD-L1 proteins expressed by cancer cells; hence, reducing the number of target checkpoint proteins that need to be blocked by checkpoint inhibitors.
This results in an elegant one-two-three punch on the destruction of cancer cells; where, Rutherrin delivers the first punch, targeting and destroying cancer cells directly, as well as the second punch, by reducing the number of PD-L1 proteins expressed. This allows immunotherapeutic drugs to deliver the third and final punch, blocking the PD-L1 proteins remaining, allowing the immune system to significantly increase their recognition of cancer cells and hence their destruction. As a result, this technological advance increases both the safety and efficacy of immunotherapy, as less treatments would be required to induce the same clinical effect.
As a primary MOA, Rutherrin, has been demonstrated clinically to destroy NMIBC, when activated by light, and preclinically to destroy GBM and Non-Small Cell Lung Cancer ("NSCLC"), when activated by x-ray radiation.
As a secondary MOA, Rutherrin, has been demonstrated preclinically to unmask cancer cells through dual immunogenic check points; specifically, CD47 (previously reported by Theralase) and now PD-L1 inhibition. This down regulation of immunogenic check points allows the cancer cell to be detected and destroyed by the immune system, resulting in a process known as Immunogenic Cell Death ("ICD"). ICD is characterized by the secretion of Damage-Associated Molecular Patterns ("DAMPs"), which are transported to the cell surface during ICD.
Calreticulin ("CRT"), one of the DAMPs found in the lumen of the endoplasmic reticulum, is translocated to the surface of dying cells, after the induction of ICD, where it functions as an "eat me" signal for the immune system.
Dr. Arkady Mandel, M.D., Ph.D., D.Sc., Chief Scientific Officer of Theralase stated, "It is one of humanity’s greatest health challenges in the 21st century, that cancer of various forms, affects and kills millions of people each and every year, without discrimination. Immunotherapy is the latest technology that attempts to harness the power of the immune system to detect and destroy cancer cells; however, these same cancer cells, treated with immunotherapy, develop mechanisms to avoid detection by the immune system, which consequently has an adverse effect on how effectively they react to therapy. In that regard, in a clinical setting, the term "resistance to immunotherapy" is applied; primary resistance denoting a failure to respond to the treatment from day one, while secondary resistance denoting a relapse following the initial response to immunotherapy. Despite remarkable scientific progress in this field, attempts to develop new strategies against cancer resistance to immunotherapy have proven difficult. We are very pleased with the results of our latest research, demonstrating that our lead drug formulation, Rutherrin, is able to maintain a therapeutic balance between various "accelerators" and "brakes" of our immune system to ensure that it is sufficiently engaged in attack against malignant cells, while avoiding destruction of healthy cells and tissues."
Roger DuMoulin-White, B.E.Sc., P.Eng., Pro.Dir., President and Chief Executive Officer of Theralase stated, "All cancer therapies, in their essence, attempt to destroy the disease, with minimal to no side effects and allow the patient a complete response with no recurrence; however, despite recent advances in the treatment of specific cancer types, many patients still struggle to respond to cancer treatments and are left with significant side effects. The PD-L1 (immune checkpoint protein) functions as a "brake" on the innate immune system, while Calreticulin ("eat me" signal) functions as an accelerator. We are very pleased to demonstrate that Rutherrin has the potential of releasing the "brake" and applying the "accelerator" to the immune system at the right time and thereby unleashing the power of our immune system to attack and destroy cancerous cells, while sparing healthy ones. By stimulating the inherent ability of our immune system to protect and defend our bodies against cancer, Rutherrin has the potential to establish an entirely new paradigm for cancer therapy."