| RRC ID |
38581
|
| Author |
Sakamoto M, Nakajima J, Murakawa T, Fukami T, Yoshida Y, Murayama T, Takamoto S, Matsushita H, Kakimi K.
|
| Title |
Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded γδTcells: a phase I clinical study.
|
| Journal |
J Immunother
|
| Abstract |
Human γδ T cells can recognize and kill non-small cell lung cancer (NSCLC) cells using the Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established clinical grade large-scale ex vivo expansion of γδ T cells from peripheral blood mononuclear cells by culturing with zoledronate and interleukin-2 (IL-2). A phase I study was conducted to evaluate safety and potential antitumor effects of re-infusing ex vivo expanded γδ T cells in patients with recurrent or advanced NSCLC. Patient's peripheral blood mononuclear cells were stimulated with zoledronate (5 μM) and IL-2 (1000 IU/mL) for 14 days. Harvested cells, mostly γδ T cells, were given intravenously every 2 weeks without additional IL-2, a total of 6 times. The cumulative number of transferred γδ T cells ranged from 2.6 to 45.1 x 10⁹ (median, 15.7×10⁹). Fifteen patients underwent adoptive immunotherapy with these γδ T cells. There were no severe adverse events related to the therapy. Immunomonitoring data showed that with increasing numbers of infusions, the number of peripheral γδ T cells gradually increased. All patients remained alive during the study period with a median survival of 589 days and median progression-free survival of 126 days. According to the Response Evaluation Criteria In Solid Tumors, there were no objective responses. Six patients had stable disease, whereas the remaining 6 evaluable patients experienced progressive disease 4 weeks after the sixth transfer. We conclude that adoptive transfer of zoledronate-expanded γδ T cells is safe and feasible in patients with NSCLC, refractory to other treatments.
|
| Volume |
34(2)
|
| Pages |
202-11
|
| Published |
2011-3-1
|
| DOI |
10.1097/CJI.0b013e318207ecfb
|
| PMID |
21304399
|
| MeSH |
Adult
Aged
Aged, 80 and over
Bone Density Conservation Agents / pharmacology
Carcinoma, Non-Small-Cell Lung / immunology
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Non-Small-Cell Lung / therapy*
Cell Proliferation / drug effects*
Cytotoxicity, Immunologic / drug effects
Diphosphonates / pharmacology*
Female
Humans
Imidazoles / pharmacology*
Immunotherapy, Adoptive*
Interleukin-2 / pharmacology
Male
Middle Aged
Neoplasm Staging
Quality of Life
T-Lymphocytes / drug effects*
T-Lymphocytes / immunology
Treatment Outcome
Zoledronic Acid
|
| IF |
2.985
|
| Times Cited |
13
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
DAUDI(RCB1640) |
