This is a new modified TIL protocol developed by Obsidian Therapeutics now open for enrollment at the Orlando Health Cancer Institute. All information provided here are from public sources and the protocol details can be found here. Please reach out to Karin Donaldson if interest in seeking this trial. This current protocol is specific for metastatic melanoma but hopefully new cohorts in other tumor types will soon come.
In the relentless battle against metastatic melanoma, the medical world has witnessed remarkable strides, particularly in the realm of Tumor-Infiltrating Lymphocytes (TIL) therapy which we are currently awaiting the FDA approval for Iovance TIL February 2024 or possibly sooner. This approach, which involves extracting and expanding a patient’s own T cells to fight cancer, has shown promise in tackling this formidable disease. However, traditional TIL therapy, despite its potential, comes with its own set of challenges, notably the requirement of high-dose IL2—a treatment known for its toxicity and complexity. But today, we stand on the cusp of a groundbreaking evolution in this therapy.
Introducing OBX-115: A Game Changer in TIL Therapy
OBX-115 represents a transformative leap in TIL therapy. This novel engineered TIL therapy is embedded with a regulated membrane-bound IL-15, which is poised to eliminate the need for concurrent IL2 therapy. Imagine these TILs as specialized soldiers, initially dormant within the body, awaiting a signal to spring into action. The introduction of OBX-115 is akin to providing these dormant soldiers with advanced, self-activating stimulation and proliferation, removing the need for external, strenuous support like IL2.
The Activation Key: Acetazolamide
The magic lies in the innovative activation mechanism of OBX-115. Acetazolamide, a medication typically known for other medical uses, plays a pivotal role here. When administered, it acts as a switch, turning on the membrane-bound IL15. This process can be likened to a dormant security system that springs to life at the flick of a switch. Once activated, these TILs begin to proliferate autonomously, attacking the cancer cells with renewed vigor and precision, all while mitigating the previously unavoidable toxic side effects associated with IL2.
The preclinical data for OBX-115 is nothing short of inspiring. It has shown enhanced potency, persistence, and anti-tumor efficacy compared to traditional un-engineered TILs combined with IL2. This is not just a step forward; it’s a leap towards a future where TIL therapy is more accessible, less exhausting for the patient, and potentially more effective. The distinct manufacturing process of OBX-115 also ensures a desirable TIL phenotype—memory T-cells and CD8+ T cells—that are less exhausted and more robust in their anti-cancer activity. For patients battling metastatic melanoma, OBX-115 could open doors to a treatment that is not only more bearable but also more efficacious. The elimination of IL2 from the treatment regimen is poised to broaden patient eligibility, inviting those who previously might have had to forego this promising therapy due to the inability to tolerate or access IL2 including elderly patients.
As we move forward with cautious optimism, the potential of OBX-115 in revolutionizing TIL therapy for metastatic melanoma patients is immense. This advancement is not merely an incremental improvement; it’s a paradigm shift, marking the dawn of a new era in the fight against cancer.
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About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.