ASCO 2026 | Development and rationale of OBX-115, an IL-15-expresesing TIL for melanoma
Allison Betof Warner, MD, Stanford University, Stanford, CA, discusses the limitations of conventional TIL therapy, which relies on high-dose IL-2 to stimulate tumor-infiltrating lymphocytes, and introduces OBX-115, a novel approach that utilizes a transgene to express membrane-bound IL-15, allowing for localized activation of immune cells without the need for systemic IL-2. OBX115 has the potential to minimize or eliminate the toxic effects associated with high-dose IL-2, thereby expanding the eligibility of patients for TIL therapy. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Conventional TIL therapy, we know that we take patients’ own tumor-infiltrating lymphocytes, expand them ex vivo in the lab, and then give them back to a patient. But that requires the use of high-dose IL-2 to stimulate those cells to proliferate and to do their work. We’ve been looking for a long time for a way to either minimize the exposure to high-dose IL-2 or actually eliminate it completely because that’s actually the most toxic part of this regimen and actually really limits the number of patients that we can treat with TIL therapy...
Conventional TIL therapy, we know that we take patients’ own tumor-infiltrating lymphocytes, expand them ex vivo in the lab, and then give them back to a patient. But that requires the use of high-dose IL-2 to stimulate those cells to proliferate and to do their work. We’ve been looking for a long time for a way to either minimize the exposure to high-dose IL-2 or actually eliminate it completely because that’s actually the most toxic part of this regimen and actually really limits the number of patients that we can treat with TIL therapy. So OBX115 takes those same TIL cells out of a patient’s tumor, inserts a transgene that expresses membrane-bound IL-15 conjugated to a drug regulation domain. At baseline, those cells express that molecule, and it degrades at baseline because that’s unstable. When we give the patient oral acetazolamide, which is just an FDA-approved diuretic medication, it stabilizes the drug regulation domain, and that then allows the membrane-bound IL-15 to translocate to the membrane. It signals in both cis and trans to activate the same cell as well as nearby NK and CD8 cells and turn them on without giving the patient systemic IL-2.
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