Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial.
BACKGROUND
Renal cell cancer and malignant melanoma are two types of cancer that are responsive to immunotherapy. In this phase I dose-escalation study, the feasibility of large-scale expansion and safety of administering ex vivo-expanded NK-92 cells as allogeneic cellular immunotherapy in patients with refractory renal cell cancer and melanoma were determined.


METHODS
Twelve patients (aged 31-74 years) were enrolled, three per cohort at cell dose levels of 1x10(8)/m(2), 3x10(8)/m(2), 1x10(9)/m(2) and 3x10(9)/m(2). One treatment course consisted of three infusions. Eleven patients had refractory metastatic renal cell cancer; one patient had refractory metastatic melanoma.


RESULTS
The NK-92 cells were expanded in X-Vivo 10 serum-free media supplemented with 500 U/mL Proleukin recombinant human interleukin-2 (rhIL-2), amino acids and 2.5% human AB plasma. Final yields of approximately 1x10(9) cells/culture bag (218-250xexpansion) over 15-17 days were achievable with >or=80% viability. Infusional toxicities of NK-92 were generally mild, with only one grade 3 fever and one grade 4 hypoglycemic episode. All toxicities were transient, resolved and did not require discontinuation of treatment. One patient was alive with disease at 4 years post-NK-92 infusion. The one metastatic melanoma patient had a minor response during the study period. One other patient exhibited a mixed response.


CONCLUSIONS
This study establishes the feasibility of large-scale expansion and safety of administering NK-92 cells as allogeneic cellular immunotherapy in advanced cancer patients and serves as a platform for future study of this novel natural killer (NK)-cell based therapy.
Arai
S
S
Rush University Medical Center, Chicago, Illinois, USA. sarai1@stanford.edu
Meagher
R
R
Swearingen
M
M
Myint
H
H
Rich
E
E
Martinson
J
J
Klingemann
H
H
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*
D016207:Cytokines