Table 3.
Trials of Adoptive NK cell therapy
Disease | Setting | Method of preparation | Cell number | Concomitant medication | n | Effect on patient outcome | |
---|---|---|---|---|---|---|---|
AML | NK-DLI for patients in first CR following chemotherapy | Apheresis followed by CD3 depletion and subsequent CD56 selection | 2.9 × 107/kg (range 0.5–8 × 107/kg) | Cyclophosphamide (day −7) Fludarabine (Day −6 to −2) |
10 | 100% 2 year event free survival | NKAML study (80) |
AML | NK-DLI for poor prognosis AML | Apheresis followed by CD3 depletion and ex-vivo stimulation with IL2 | 1 ×105 – 2 ×107 | Low dose cyclophosphamide/melphalan vs. High dose cyclophosphamide and fludarabine. IL2 given to all patients |
19 | Complete haematological remission in 5 of 19 patients | (42) |
Myeloma | Haploidentical KIR ligand mismatched NK- DLI followed by delayed autologous stem cell transplant | Apheresis followed by CD3 depletion | 2.4×107/kg | Melphalan and fludarabine conditioning | 10 | Near CR in 50% of patients | (81) |
CD20+ NHL | NK-DLI for refractory disease (more than 2 salvage therapies) | Apheresis followed by CD3 depletion | 2.1 × 107/kg (range 0.2–40 × 107/kg) | Fludarabine (25mg/m2) Cyclophosphamide (60mg/m2) |
6 | 4 objective remissions 2 complete remissions |
(83) |
Not stated | Allogeneic stem cell transplant | Apheresis followed by CD3 depletion and subsequent CD56 selection | 1.2×107/kg | Not stated | 14 | NK infusions well tolerated, aside one case of grade IV | (131) |
High risk myeloid malignancies | Graft failure/mixed donor chimerism following allogeneic (haploidentical) stem cell transplant | Apheresis followed by CD3 depletion and subsequent CD56 selection | 1.61 × 107/kg (range 0.21–2.2) | None | 5 | Reversal of mixed donor chimerism in 2/5 | (132) |
Not stated | Following 3-6/6 HLA matched T cell-depleted nonmyeloablative allogeneic transplant | Apheresis followed by CD3 depletion and CD56 selection | 1.06 × 107/kg | Infusion performed 6–8 weeks following fludarabine conditioned allogeneic transplant with alemtuzumab | 30 | Improved T cell recovery and duration of remission | (133) |
Breast and ovarian carcinoma | NK DLI for patients with relapsed disease | Apheresis followed by CD3 depletion | 2.17 × 107/kg | Fludarabine and cyclophosphamide Total body irradiation in 7 patients IL2 x6 doses s.c. post DLI |
20 | TBI improved longevity of NK engraftment | (134) |
Colorectal carcinoma, hepatocellular carcinoma, renal cell carcinoma and B-CLL | Previous allogeneic BMT with donor derived NK cells | Apheresis followed by ex vivo expansion with IL-2 | 0.1 × 107 followed by two doses mean 3.3 × 107 | Variable; some patients received sc IL-2 | 5 | Minor responses in 2 patients | (135) |
Advanced non-small cell lung cancer | NK-DLI after chemotherapy | CD56 selection followed by culture with IL-15 | 0.46 × 107/kg (range 0.2–2.9) | 2–4 doses of NK DLIs given 2 days after chemotherapy (carboplatin-paclitaxel most commonly used) | 16 | Trend to better OS in subgroup receiving 4 doses of NK cells | (136) |
Advanced renal cell carcinoma and malignant melanoma | NK-92 cell line infusion | Expansion of NK lymphoma cell line | Up to 3 × 109/m2 | Cell infusion alone | 12 | Infusion well tolerated. Possible response in 2 patients | (86) |