OX40 Agonist: Revving Up Immune Activation


The OX40 receptor, scientifically known as CD134, is part of the tumor necrosis factor receptor superfamily. It plays a pivotal role as a co-stimulatory molecule expressed on activated T cells and antigen-presenting cells. Unlike many of the prevailing immunotherapy agents like anti-PD-1 and anti-CTLA-4, which act as the brakes on the immune system, OX40 is more like the gas pedal. OX40 serves a dual purpose: it releases the brakes, i.e., regulatory cells, while simultaneously accelerating T cell activation. Unlike other therapies that block receptors, OX40 agonists activate these receptors. In essence, OX40 agonists remove the brakes and hit the gas simultaneously.

A recent Stanford study garnered considerable attention, emphasizing several critical factors. First, the study highlighted the importance of combination therapies for optimal results. In this case, it involved a combination of a Toll-like receptor (TLR) agonist with an OX40 agonist. Second, the study underscored the significance of intra-tumoral treatments, where medications are injected directly into the tumor. This approach offers advantages, including reduced dosage and costs, which is crucial as the healthcare system already struggles with the expenses associated with current treatments. Patients deserve access to these life-saving medications, and intra-tumoral treatment could be the key.

Currently, we are treating human patients with various cancer types using the OX40/CpG agonist injected directly into tumors, similar to the Stanford mouse study. Our results have been exceptionally promising. To enhance the outcomes for human patients, we have incorporated the CTLA-4 inhibitor Yervoy, further enhancing the effectiveness of OX40 agonists. We are excited to present and publish our initial results from this approach in 2019, paving the way for a potential revolution in cancer treatment.

Reference: Jason R. Williams, 15 Oct 2019, The Immunotherapy Revolution: The Best New Hope For Saving Cancer Patients’ Lives, https://williamscancerinstitute.com/the-immunotherapy-revolution