Table 1.
Selected clinical trials using CIK (without associated DCs) and NK cells adoptive therapy
| Reference | Study type | Patients | Treatment | Source | Dose-administered | Preparation | Efficacy | Toxicity |
|---|---|---|---|---|---|---|---|---|
| Wu, 2008 [30] | Randomized controlled trial | 59 NSCLC, stage IIIB–IV | CIK + CT vs CT | Autologous PBMCs | 1 × 10*9 × 5 (every 48 h), 5d after CT |
IL-1α, γIFN, IL-2, anti-CD3 |
ORR 45% vs 43%, DCR 90% vs 66%, mPFS 6.7 m vs 4.7 m, mOS 15 m vs 11 m |
Temporary fever and headache |
| Niu, 2011 [33] | Randomized controlled trial | 40 advanced solid tumors: 15 NSCLC | CIK + 2nd line CT vs 2nd line CT | Cord-blood | 9 × 10*9 × 6 (within 12d), 1w after CT | γIFN, IL-2, IL-1, anti-CD3 | ORR 30% vs 15%, DCR 80% vs 70%, mPFS 3.5 m vs 2.0 m, mOS 11.2 m vs 7.5 m | Grade 1–2 flu-like symptoms |
| Li, 2012 [31] | Phase II | 100 NSCLC stage I–IIA, 74 NSCLC stage IIIB-IV | CIK + CT vs CT | Autologous PBMCs | 1 × 10*10 on d15 and d17 of each CT cycle |
IL-1α, γIFN, IL-2, anti-CD3 |
Early-stage: mOS 73 m vs 53 m Advanced stage: mOS 24 m vs 10 m, mPFS 13 m vs 6 m |
No data |
| Jin, 2014 [32] | Randomized controlled trial | 943 NSCLC, stage I–III | CIK + standard treatment vs standard treatment | Autologous PBMCs | 2–6 × 10*9 × 3 consecutive days, 6 courses (18 m) | γIFN, IL-2, anti-CD3 | mOS 48 m in the CIK group vs 36 m, 56.2% recurrence vs 78.6% | No data |
| Iliopoulou, 2010 [49] | Phase I | 16 NSCLC, stage IIIB–IV | NK + 1st or 2nd line CT | Allogeneic (haploidentical -KIR mismatch relative donors), peripheral blood | 0.2–2 × 10*6/kg (× 2–4 doses) | CD56 isolation (microbeads), IL-15, HC | 2 PR, 6 SD, 7 PD, mPFS 5.5 m, mOS 15 m | No side effect |
| Tonn, 2013 [53] | Phase I | 13 advanced or metastatic solid tumors: 3 SCLC, 1 NSCLC | NK | Allogeneic, NK-92 cell line | 1–10 × 10*9 cells/m2, 2 infusions, 48 h apart | IL-2 | Lung cancer: 2 PR, 1 SD (2y), 1 PD | No side effect |
| Lin, 2020 [50] | Randomized controlled trial | 109 NSCLC, stage IIIB-IV, PDL1 ≥ 1%, PD after CT/ TKI | NK + Pembrolizumab vs Pembrolizumab without NK | Allogeneic (haploidentical -KIR mismatch), peripheral blood | 3 × 10*9 (3 infusions/2 weeks, 2–6 cycles) | “HANK cell culture medium” | ORR 36.4% (20 PR, 30 SD, 5 PD) vs 18.5% (10 PR, 29 SD, 15 PD), reduction in CTCs, mPFS 6.5 m (HR 0.58), mOS 15.5 m (HR 0.60) | Adverse events attributable to Pembrolizumab (no difference between the 2 groups) |
| Multhoff, 2020 [54] | Phase II | 16 NSCLC, stage IIIA/B, after RCT, mHsp70 + | NK | Autologous, peripheral blood | 10*8–10*9 (/2–6 weeks, 4 cycles) | TKD peptide, IL-2 | 1 CR, 1 PR, 2 SD, 2 PD in the treatment group vs 1 PR, 1 SD, 5 PD in the control group | No adverse event attributed to NK cells |
| Chawla, 2020 [55] | Phase I, ongoing | 1 NSCLC, 5 sarcomas, 1 CRC | NK | Autologous | 1–2 × 10*9 (/week, 5 cycles) | SNK01 preparation | SD as best overall response in the first 3 patients | No adverse event in the first 3 patients |
| Kim, 2020 [56] | Phase I/II, ongoing | 14 NSCLC, stage IV, PDL1 + | NK + Pembrolizumab vs Pembrolizumab without NK | Autologous | 2–4 × 10*9 (/week, 6 cycles) | SNK01 preparation | 4 PR in the first 6 patients in the treatment group vs 3 PD in the control group | No adverse event in the first 6 patients |
CT chemotherapy, TKI tyrosine kinase inhibitor, RCT adiochemotherapy, CRC colorectal cancer, HC hydrocortisone, CR complete response, PR partial response, SD stable disease, PD progressive disease, mOS = median overall survival, mPFS median progression-free survival, CTCs circulating tumor cells, anti-CD3 anti-CD3 monoclonal antibody