The absolute number of naïve T cell populations in patients predicts response to CIK cell therapy.
Based upon the above results that patients with a high absolute number of naïve CD4+ and naïve CD8+ cells could produce more CIK cells and maintain sustained antitumor activity, we compared the absolute number of naïve T cells to healthy donors (Mean = 298 in naïve CD4+ and 156 in naïve CD8+ cells) by dividing the patients into groups with high naïve T cell counts (15 of 68) and low naïve T cell counts (53 of 68). In the overall population, the ORR was 13.2% (9 of 68), while the ORR in patients with high naïve T cell counts was 40% (6 of 15) compared to 5.7% (3 of 53) in patients with low naïve T cell counts. Moreover, 4.4% of patients with high numbers of naïve T cells (3 of 68) showed CR and 11.8% (8 of 68) showed PR, but only one patient showed CR among the low naïve T cell-count patients. In addition, 23.5% (16 of 68) of patients achieved SD and a disease control rate (DCR) of 42.6% (29 of 68). Two NSCLC patients with high numbers of naïve T cells had greater than 50% target lesion reduction by 18 weeks (Figure 5C), and a patient with high naïve T cell counts who experienced multiple brain metastases achieved CR after chemotherapy and treatment with radio frequency ablation (Figure 5C). Among responders, 26.5% (18 of 68 patients) had responded by month 4, including 21.6% (11 of 51) with low naïve T cell counts and 41.2% (7 of 17) with high counts. Among responders, 22% of responses (4 of 18 patients) were ongoing, with response durations ranging from 4 to 14.5+ months. Among patients with high naïve T cell counts, 42.9% (3 of 7) displayed an ongoing response, including a liver cancer and NSCLC patient with PR who achieved an antitumor response for more than 10 months after eight cycles of autologous CIK cell treatment. In contrast, only one patient with a low naïve T cell count achieved an ongoing response after eight cycles of autologous CIK cell treatment (Figure 5D). The median PFS was significantly longer in 51 patients with low naïve T cell counts (5 months; 95% CI 1‒9 months) than in 17 patients with high numbers of naïve T cells (8 months; 95% CI 2–14.5 months; P<0.0026; Figure 5E).