CIK cell preparations
Blood (80 mL) was obtained from heparinized peripheral blood of all the patients. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll- Hypaque gradient centrifugation. Cells were cultured in X-15 medium containing 2% autologous serum and adhered for 1 hour. The suspension cells were stimulated with 1000 U/ml IFN-gamma for the first 24 hours, then induced into CIK cells with 100 ng/ml OKT-3, 1000 U/ml RHIL-2 and 100 U/ml IL-1α.
At 14 days, the fraction of CIK cells were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Vitalities of CIKs determined by trypan blue staining, CIKs activity and CD3+CD45+ T cells were accounted for more than 95% and 90% of total cells. Then, autologous CIK (1.0-1.5×1010 cells) were transferred to patients via intravenous infusion.
All patients received intravenous infusions of autologous CIK cells. All participants received at least eight cycles of infusions (four cycles at weekly intervals followed by four cycles every 2 weeks) or received cycles until they experienced disease progression or unacceptable adverse events (AEs) or withdrew consent.
The most common AEs arising from treatment with CIK cells during the study were fever; all fevers rose no higher than 380C and spontaneously resolved within 12 hours. Additional AEs observed were decreased albumin levels, increased serum AST and ALT levels, anemia, leukopenia, thrombocytopenia, chills, hypothyroidism and vitiligo. All grades of treatment-related AEs occurred in 25 of 68 patients (36.8%), and most of the cytotoxicity assay results were grade 1 or 2 (22 of 25 patients, 88%). Grade 3 or 4 treatment- related AEs were observed in only 3 patients (12%). One NSCLC and one CRC patient were observed with grade 3 fever, and grade 3 chill was observed in another HCC patient during treatment.
In the overall population, the objective- response rate (ORR) was 13.2% (9 of 68), while the ORR in patients with high naive T cell counts was 40% (6 of 15) compared to 5.7% (3 of 53) in patients with low naive T cell counts.
4.4% of patients with high numbers of naive T cells (3 of 68) showed CR and 11.8% (8 of 68) showed PR, but only one patient showed CR among the low naive 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 naive T cells had greater than 50% target lesion reduction by 18 weeks, and a patient with high naive T cell counts who experienced multiple brain metastases achieved CR after chemotherapy and treatment with radio frequency ablation. Among responders, 26.5% (18 of 68 patients) had responded by month 4, including 21.6% (11 of 51) with low naive 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 naive 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. The median PFS was significantly longer in 51 patients with low naive T cell counts (5 months; CI 1-9 months) than in 17 patients with high numbers of naive T cells (8 months; CI 2–14.5 months).
These results suggested that amplification of CIK cells from patients with high numbers of naive T cells significantly enhanced effector function, enhanced proliferative capacity and improved anti-tumor efficacy in vivo. The patients with high absolute numbers of naive T cells in circulating blood had a better response to ACT, which demonstrated the potential of using pretreatment biomarkers of response in ACT.
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Scientific article publishing date 9/10/2020
Immucura identifier BSC21_284EN