Monitoring of a new approach of immunotherapy with allogenic 111In-labelled NK cells in patients with renal cell carcinoma

Abstract

The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3-7 x 10(8) NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach.

NK cell-based immunotherapy for malignant diseases

“…NK cells were labeled with a 111 In radiotracer during NK cell therapy, and SPECT images provided evidence for the activity, redistribution and tracer accumulation with high sensitivity, indicating an effective immunotherapeutic approach. 191 However, many limitations for PET/SPECT still exist, including high cost, low resolution (1-2 mm), radiation exposure, tracer decay and limited ability for follow-up studies (2-3 h for the 18 FDG radiotracer or 4-7 days for 111 In). The low resolution issue may be improved by integrating the PET/SPECT images with highresolution CT images (200-400 mm), which is currently being investigated.…”

19F-MRI for monitoring human NK cellsin vivo

“…8,9 In vivo studies using immunocompetent mice or xenogeneic mouse models, mouse NK cells or human NK cell lines (NK92) have been labeled with the radionuclides 18 FDG or 11 C-methyl iodide for detection by PET. Allogeneic or autologous human NK cells were also labeled ex vivo with the gamma emitting radioisotope indium-111 oxine ( 111 In) for detection by SPECT in patients with renal cell carcinoma 49,50 and in patients with colon cancer with liver metastasis. 51 In the renal cell carcinoma patients, the NK cells initially accumulated to the lungs, after intravenous injection, and redistributed to the liver and metastatic tumors (lungs and livers) within 24 h. 49,50 Conversely, in the study with the colon cancer patients, NK cells were only detected within the tumor after intra-arterial delivery of the NK cells.…”

“…Allogeneic or autologous human NK cells were also labeled ex vivo with the gamma emitting radioisotope indium-111 oxine ( 111 In) for detection by SPECT in patients with renal cell carcinoma 49,50 and in patients with colon cancer with liver metastasis. 51 In the renal cell carcinoma patients, the NK cells initially accumulated to the lungs, after intravenous injection, and redistributed to the liver and metastatic tumors (lungs and livers) within 24 h. 49,50 Conversely, in the study with the colon cancer patients, NK cells were only detected within the tumor after intra-arterial delivery of the NK cells. 51 However, the inability to distinguish from cell-bound versus free 111 In might give false positive for the true localization of NK cells.…”

Allogeneic transplantation of hematopoietic stem cells: Perspectives and alternatives, own experience

“…Инфузия донорских NK-клеток уменьшает также и риск рецидива заболевания, как показано на примере лечения ОМЛ. В последнее время активно изучаются возможности иммунотера-пии гемобластозов и солидных опухолей донорскими NK-клетками без проведения собственно алло-ТГСК [63][64][65] или совместно с ауто-ТГСК -лечение реци-дивирующей ММ [61].…”