Based on preclinical cancer models that showed potent antitumor activity against multiple tumor types of anti-OX40 antibody, which is dependent on both CD4+ and CD8+ T-cells [71,72,73,74], a phase I study showed that OX40 agonist antibody (9B12) induced the regression of at least one metastatic lesion in 40% (12/30) patients with advanced cancer with acceptable toxicity (most toxicity was grade 1 or 2). Here, CD4 is linked to cancer.