Higher doses may have a negative impact on tumor efficacy due to the risk of T-cell overstimulation and exhaustion, or receptor binding and oligomerization.28 A similar observation has been made with other OX40 agonists,27 29 and this was the rationale for not continuing further dose escalation in our study when the MTD was not reached. The gene discussed is TNFRSF4; the disease is neoplasm.