TY - JOUR
T1 - Highly activated ex vivo-expanded natural killer cells in patients with solid tumors in a phase I/IIa clinical study
AU - Nagai, Kazuhiro
AU - Harada, Yui
AU - Harada, Hiroshi
AU - Yanagihara, Katsunori
AU - Yonemitsu, Yoshikazu
AU - Miyazaki, Yasushi
N1 - Funding Information:
K. Nagai received funding for this research from Tella Inc.
Funding Information:
The Authors thank the patients who participated in this clinical trial and the referring physicians who performed concomitant therapy and provided follow-up information, and the technologists of Nagasaki University Hospital who support this clinical study. This study was funded by Tella Inc., Tokyo, Japan.
PY - 2020/10
Y1 - 2020/10
N2 - Background: We previously developed a novel technique for expanding highly activated and purified natural killer (NK) cells able to maximize the theoretical activation potential of NK cells; thus, we named this cell population zenithal-NK (ZNK). Aim: To evaluate the safety, feasibility, and preliminary efficacy of autologous ZNK cells in patients with different types of advanced cancer with measurable solid lesions. Patients and Methods: In this phase I/IIb first-inhuman, open-label, dose-escalation study (trial registration ID: UMIN-000011555), eligible patients received ZNK cells intravenously starting from 106 to 108 cells/patient/dose at 2-week dosing intervals. A maximum of six cycles were allowed. Safety and survival analyses were also carried out for cases that were excluded and never administered ZNK cells. Results: As of April 20, 2017, a total of nine patients were enrolled in this study, with one recruited twice. Overall, neither grade 2 or higher toxicities (Common Terminology Criteria for Adverse Events v5.0) caused by cell administration, nor adverse events causing discontinuation of protocol treatment were found. In four cases, the number of administered ZNK cells was increased to 108 cells/body/dose without any serious dose-limiting toxicity; the maximally tolerated dose was therefore considered to be at least 108 cells. The overall response rate was 40.0% in 10 net cases, one of partial response and three of stable disease, and the patient with partial response is still alive after 4 year’s observation. Conclusion: These results demonstrate that autologous ZNK cells are safe and well-tolerated in patients with different types of advanced solid tumors. Clinical studies using similarly active ZNK cells from human leukocyte antigen/killer cell immunoglobulin-like receptor-mismatched healthy donors under Good Manufacturing Practice-compliant manufacturing, and with modified treatment regimen, i.e. doses and frequencies, are warranted for further investigation to show the potential of ZNK cells in such patients.
AB - Background: We previously developed a novel technique for expanding highly activated and purified natural killer (NK) cells able to maximize the theoretical activation potential of NK cells; thus, we named this cell population zenithal-NK (ZNK). Aim: To evaluate the safety, feasibility, and preliminary efficacy of autologous ZNK cells in patients with different types of advanced cancer with measurable solid lesions. Patients and Methods: In this phase I/IIb first-inhuman, open-label, dose-escalation study (trial registration ID: UMIN-000011555), eligible patients received ZNK cells intravenously starting from 106 to 108 cells/patient/dose at 2-week dosing intervals. A maximum of six cycles were allowed. Safety and survival analyses were also carried out for cases that were excluded and never administered ZNK cells. Results: As of April 20, 2017, a total of nine patients were enrolled in this study, with one recruited twice. Overall, neither grade 2 or higher toxicities (Common Terminology Criteria for Adverse Events v5.0) caused by cell administration, nor adverse events causing discontinuation of protocol treatment were found. In four cases, the number of administered ZNK cells was increased to 108 cells/body/dose without any serious dose-limiting toxicity; the maximally tolerated dose was therefore considered to be at least 108 cells. The overall response rate was 40.0% in 10 net cases, one of partial response and three of stable disease, and the patient with partial response is still alive after 4 year’s observation. Conclusion: These results demonstrate that autologous ZNK cells are safe and well-tolerated in patients with different types of advanced solid tumors. Clinical studies using similarly active ZNK cells from human leukocyte antigen/killer cell immunoglobulin-like receptor-mismatched healthy donors under Good Manufacturing Practice-compliant manufacturing, and with modified treatment regimen, i.e. doses and frequencies, are warranted for further investigation to show the potential of ZNK cells in such patients.
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U2 - 10.21873/anticanres.14583
DO - 10.21873/anticanres.14583
M3 - Article
C2 - 32988894
AN - SCOPUS:85092121528
VL - 40
SP - 5687
EP - 5700
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 10
ER -